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ObjectivesDuring the COVID-19 pandemic, addiction treatment services received official guidance asking them to limit face-to-face contact with patients and to prescribe opioid agonist treatment (OAT) medication flexibly. With the aim for most patients to receive take-home supplies for self-administration rather than attendance for observed daily dosing.DesignThis was a theory-driven, clinically applied qualitative study, with data for thematic analysis collected by semi-structured, audio-recorded, telephone interviews.ParticipantsTwenty-seven adults (aged ≥18 years) enrolled in sublingual (tablet) buprenorphine and oral (liquid) methadone OAT.SettingCommunity addictions centre in the London Borough of Lambeth operated by South London and Maudsley NHS Trust.ResultsThree major themes were identified: (1) dissatisfaction and perceived stigma with OAT medication dispensing arrangements before the pandemic; (2) positive adaptations in response to COVID-19 by services; (3) participants recommended that, according to preference and evidence of adherence, OAT should be personalised to offer increasing medication supplies for self-administration from as early as 7 days after commencement of maintenance prescribing.ConclusionsIn an applied qualitative study of patients enrolled in OAT during the COVID-19 pandemic, participants endorsed their opportunity to take medication themselves at home and with virtual addiction support. Most patients described a preference for self-administration with increased dispensing supplies, from as early as 7 days into maintenance treatment, if they could demonstrate adherence to their prescription.…

ObjectivesTo evaluate the frequency of knowledge and attitudes towards dengue prevention among the Peruvian population, as well as the sociodemographic factors associated with reported knowledge and attitude outcomes.Design/settingA cross-sectional study was conducted, based on information from the National Survey of Budget Programs of Peru, 2019.ParticipantsWe included 57 829 respondents with a mean age of 40.3±17.4 years, of whom 52.8% were women and 87.6% were from urban areas.Primary and secondary outcomesKnowledge about dengue infection (transmission, symptoms, importance of going to a health centre and not self-medicating) and preventive attitudes to avoid infection.ResultsOf all the respondents, 36.2% (n=23 247) presented good knowledge about dengue and 11.6% (n=7890) had a higher number of preventive attitudes (≥3 attitudes). In the multivariate regression analysis, we found that being female (for knowledge: aPR (adjusted prevalence ratio): 1.03; 95% CI 1.02 to 1.03; and for attitude: aPR: 1.02; 95% CI 1.01 to 1.02), being married/cohabiting (for knowledge: aPR: 1.02; 95% CI 1.00 to 1.03; and for attitude: aPR: 1.01; 95% CI 1.00 to 1.02) and residing in the jungle (for knowledge: aPR: 1.14; 95% CI 1.12 to 1.16; and for attitude: aPR: 1.09; 95% CI 1.07 to 1.11) were associated with better knowledge and more preventive attitudes. In addition, we found that being an adolescent (for knowledge: aPR: 0.97; 95% CI 0.96 to 0.99; and for attitude: aPR: 0.99; 95% CI 0.97 to 0.99), and belonging to the Quechua ethnic group (for knowledge: aPR: 0.93; 95% CI 0.91 to 0.94; and for attitude: aPR: 0.98; 95% CI 0.97 to 0.99) were associated with a lower proportion of adequate knowledge and fewer preventive attitudes.ConclusionsOur study found a high proportion of poor knowledge and few preventive attitudes towards dengue in the Peruvian population. That highlights the requirement to implement national strategies to educate people about dengue and promote preventive attitudes, considering the factors found.…

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Publication date: Available online 20 March 2023Source: ImmunityAuthor(s): Mina Yang, Haojie Jiang, Chen Ding, Lin Zhang, Nan Ding, Guoming Li, Fei Zhang, Jing Wang, Liufu Deng, Junling Liu, Yanyan Xu…

Bacteria belonging to the genus Dickeya (formerly Erwinia chrysanthemi) are responsible for causing disease in numerous agricultural crops and ornamental plants globally. Within the 12 species that currently comprise this recently emerging bacterial genus, Dickeya solani is considered one of the most important bacterial phytopathogens worldwide and for research in molecular plant pathology. D. solani produces a broad spectrum of plant-cell-wall-degrading enzymes (PCWDEs), including pectinases, cellulases, and proteases, that are secreted through Type I (T1SS) and Type II (T2SS) secretion systems and act as key virulence factors allowing the bacterium to proliferate in plant tissues, liberating nutrients from dead cells.

by Hyun-il Shin, Kwang-Jae Cho, Min-Sik Kim, Young-Hoon JooBackground Human papilloma virus (HPV)-related tonsil cancer is associated with favorable outcomes. Objective The purpose of this study was to define factors affecting distant metastasis in patients with surgically treated HPV-positive tonsil cancer. Methods The present study enrolled 76 patients diagnosed with HPV-positive tonsil cancer who underwent primary surgery between January 2010 and December 2021. Results Twelve (15.7%) patients experienced a distant failure with a median follow-up time of 43 months. Sites of distant metastasis included the lung (n = 10), liver (n = 1), and brain (n = 1). Upon multivariate analysis, an advanced T stage (odds ratio [OR]: 13.94, 95% confidence interval [CI]: 1.29–149.863, p = 0.003) and margin involvement (OR: 5.96, 95% CI: 1.33–26.76, p = 0.02) were independent predictors of distant metastases. The five-year disease-specific survival for the entire cohort was 85%. The multivariate analysis confirmed that distant metastasis (hazard ratio [HR]: 12.688, 95% CI: 3.424–47.016; p < 0.001) and margin involvement (HR: 6.243; 95% CI: 1.681–23.191; p = 0.006) were significant factors associated with the five-year disease-specific survival. Conclusion HPV-positive tonsil cancer patients with an advanced T stage and a positive surgical margin have a substantial risk of distant metastases. Distant metastasis and margin involvement are factors that affect their survival.…

by Karl O. Mäki, Linda C. Karlsson, Johanna K. Kaakinen, Philipp Schmid, Stephan Lewandowsky, Jan Antfolk, Anna SoveriIndividually tailored vaccine hesitancy interventions are considered auspicious for decreasing vaccine hesitancy. In two studies, we measured self-reported format preference for statistical vs. anecdotal information in vaccine hesitant individuals, and experimentally manipulated the format in which COVID-19 and influenza vaccine hesitancy interventions were presented (statistical vs. anecdotal). Regardless of whether people received interventions that were in line with their format preference, the interventions did not influence their vaccine attitudes or vaccination intentions. Instead, a stronger preference for anecdotal information was associated with perceiving the material in both the statistical and the anecdotal interventions as more frustrating, less relevant, and less helpful. However, even if the participants reacted negatively to both intervention formats, the reactions to the statistical interventions were consistently less negative. These results suggest that tailoring COVID-19 and influenza vaccine hesitancy interventions to suit people’s format preference, might not be a viable tool for decreasing vaccine hesitancy. The results further imply that using statistics-only interventions with people who hold anti-vaccination attitudes may be a less risky choice than using only anecdotal testimonies.

by Nompilo Moyo, Ee Laine Tay, James M. Trauer, Leona Burke, Justin Jackson, Robert J. Commons, Sarah C. Boyd, Kasha P. Singh, Justin T. DenholmBackground Regionality is often a significant factor in tuberculosis (TB) management and outcomes worldwide. A wide range of context-specific factors may influence these differences and change over time. We compared TB treatment in regional and metropolitan areas, considering demographic and temporal trends affecting TB diagnosis and outcomes. Methods Retrospective analyses of data for patients notified with TB in Victoria, Australia, were conducted. The study outcomes were treatment delays and treatment outcomes. Multivariable Cox proportional hazard model analyses were performed to investigate the effect of regionality in the management of TB. Six hundred and eleven (7%) TB patients were notified in regional and 8,163 (93%) in metropolitan areas between 1995 and 2019. Of the 611 cases in the regional cohort, 401 (66%) were overseas-born. Fifty-one percent of the overseas-born patients in regional Victoria developed TB disease within five years of arrival in Australia. Four cases of multidrug-resistant tuberculosis were reported in regional areas, compared to 97 cases in metropolitan areas. A total of 3,238 patients notified from 2012 to 2019 were included in the survival analysis. The time follow-up for patient delay started at symptom onset date, and the event was the presentation to the healthcare centre. For healthcare system delay, follow-up time began at the presentation to the healthcare centre, and the event was commenced on TB treatment. Cases with extrapulmonary TB in regional areas have a non-significantly longer healthcare system delay than patients in metropolitan (median 64 days versus 54 days, AHR = 0.8, 95% CI 0.6–1.0, P = 0.094). Conclusion Tuberculosis in regional Victoria is common among the overseas-born population, and patients with extrapulmonary TB in regional areas experienced a non-significant minor delay in treatment commencement with no apparent detriment to treatment outcomes. Improving access to LTBI management in regional areas may reduce the burden of TB.…

by Stefano Perni, Bsmah Bojan, Polina ProkopovichBackground Prosthetic joint infection (PJI) is a serious complication after joint replacement surgery and it is associated with risk of mortality and morbidity along with high direct costs. Methods The Clinical Practice Research Datalink (CPRD) data were utilized to quantify PJI incidence after hip or knee replacement up to 5 years after implant and a variety of risk factors related to patient characteristics, medical and treatment history along with characteristics of the original surgery were analyzed through Cox proportional hazard. Results 221,826 patients (individual joints 283,789) met all the inclusion and exclusion criteria of the study; during the study follow-up period (5 years), 707 and 695 PJIs were diagnosed in hip and knee, respectively. Patients undergoing joint replacement surgery during an unscheduled hospitalization had greater risk of PJI than patients whose surgery was elective; similarly, the risk of developing PJI after a secondary hip or knee replacement was about 4 times greater than after primary arthroplasty when adjusted for all other variables considered. A previous diagnosis of PJI, even in a different joint, increased the risk of a further PJI. Distribution of average LoS per each hospitalization caused by PJI exhibited a right skewed profile with median duration [IQR] duration of 16 days [8–32] and 13 days [7.25–32] for hip and knee, respectively. PJIs causative micro-organisms were dependent on the time between initial surgery and infection offset; early PJI were more likely to be multispecies than later (years after surgery); the identification of Gram- pathogens decreased with increasing post-surgery follow-up. Conclusions This study offers a contemporary assessment of the budgetary and capacity (number and duration of hospitalizations along with the number of Accident and Emergency (A&E) visits) posed by PJIs in UK for the national healthcare system (NHS). The results to provide risk management and planning tools to health providers and policy makers in order to fully assess technologies aimed at controlling and preventing PJI. The findings add to the existing evidence-based knowledge surrounding the epidemiology and burden of PJI by quantifying patterns of PJI in patients with a relatively broad set of prevalent comorbidities.…

by Steven M. Goodreau, Kevin P. Delaney, Weiming Zhu, Dawn K. Smith, Laura M. Mann, Travis H. Sanchez, Deven T. Hamilton, Karen W. HooverThe COVID-19 pandemic has disrupted HIV prevention, care, and transmission opportunities. This likely varies by geography, given differences in COVID-19 burden and mandates over time, and by age, given different likelihoods of severe COVID-19 consequences. We consider changes in sexual behavior, HIV testing, pre-exposure prophylaxis (PrEP) use and antiretroviral therapy (ART) use among men who have sex with men (MSM) over the first year of the COVID-19 epidemic, comparing the Atlanta metropolitan area and New York City (NYC). We use two continuous time-series datasets and one panel dataset, assessing changes over time within city and comparing across cities, and disaggregate major findings by age. For clinical results, ART use showed by far the smallest reductions, and testing the largest. Disruptions occurred concurrently between cities, despite the major wave of COVID-19, and government mandates, occurring later in Atlanta. Test positivity increased in NYC only. In both cities, younger MSM saw the greatest reductions in testing and PrEP use, but the smallest in sexual behavior. Reduced clinical service usage would be unconcerning if stemming solely from reductions in exposure; however, the patterns for young MSM suggest that the COVID-19 epidemic likely generated new conditions for increased HIV transmission, especially in this cohort.

by Branly-Natalien Nguena-Dongue, Joseph Tchamgoue, Yvan Anderson Ngandjui Tchangoue, Paul Keilah Lunga, Kouipou Rufin Marie Toghueo, Menkem Elisabeth Zeuko`o, Yanick Kevin Dongmo Melogmo, Jean Claude Tchouankeu, Simeon Fogue Kouam, Boyom Fabrice FekamStaphylococcus aureus, the causative agent of many infectious diseases has developed resistance to many antibiotics, even chloramphenicol which was the essential antibiotic recommended for the treatment of bacterial infection. Thus, other alternatives to fight against S. aureus infections are necessary; and combinatory therapy of antibiotics with natural compounds is one of the approaches. This study evaluated the activity of the combination of mallotojaponin B and chloramphenicol against Methicillin-resistant Staphylococcus aureus (MRSA). Antibacterial activities were evaluated by broth microdilution and the checkerboard methods. Modes of action as time-kill kinetic, Nucleotide leakage, inhibition and eradication of biofilm, and loss of salt tolerance were evaluated. Cytotoxicity was evaluated on Vero and Raw cell lines. Mallotojaponin B showed good activity against MRSA with a MIC value of 12.5 μg/mL. MRSA showed high resistance to chloramphenicol (MIC = 250 μg/mL). The combination produced a synergistic effect with a mean FICI of 0.393. This combination was bactericidal, inducing nucleotide leakage, inhibiting biofilm formation, and eradicating biofilm formed by MRSA. The synergic combination was non-cytotoxic to Vero and Raw cell lines. Thus, the combination of mallotojaponin B and chloramphenicol could be a potential alternative to design a new drug against MRSA infections.

by Shannon L. Reynolds, Harvey W. Kaufman, William A. Meyer III, Chris Bush, Oren Cohen, Kathy Cronin, Carly Kabelac, Sandy Leonard, Steve Anderson, Valentina Petkov, Douglas Lowy, Norman Sharpless, Lynne PenberthyThis retrospective observational study aimed to gain a better understanding of the protective duration of prior SARS-CoV-2 infection against reinfection. The objectives were two-fold: to assess the durability of immunity to SARS-CoV-2 reinfection among initially unvaccinated individuals with previous SARS-CoV-2 infection, and to evaluate the crude SARS-CoV-2 reinfection rate and associated risk factors. During the pandemic era time period from February 29, 2020, through April 30, 2021, 144,678,382 individuals with SARS-CoV-2 molecular diagnostic or antibody test results were studied. Rates of reinfection among index-positive individuals were compared to rates of infection among index-negative individuals. Factors associated with reinfection were evaluated using multivariable logistic regression. For both objectives, the outcome was a subsequent positive molecular diagnostic test result. Consistent with prior findings, the risk of reinfection among index-positive individuals was 87% lower than the risk of infection among index-negative individuals. The duration of protection against reinfection was stable over the median 5 months and up to 1-year follow-up interval. Factors associated with an increased reinfection risk included older age, comorbid immunologic conditions, and living in congregate care settings; healthcare workers had a decreased reinfection risk. This large US population-based study suggests that infection induced immunity is durable for variants circulating pre-Delta predominance.

by Kenny J. X. Lau, Elena S. Gusareva, Irvan Luhung, Balakrishnan N. V. Premkrishnan, Anthony Wong, Tuang Yeow Poh, Akira Uchida, Elaine L. Oliveira, Daniela I. Drautz-Moses, Ana Carolina M. Junqueira, Stephan C. SchusterThe analysis of phyllosphere microbiomes traditionally relied on DNA extracted from whole leaves. To investigate the microbial communities on the adaxial (upper) and abaxial (lower) leaf surfaces, swabs were collected from both surfaces of two garden plants, Rhapis excelsa and Cordyline fruticosa. Samples were collected at noon and midnight and at five different locations to investigate if the phyllosphere microbial communities change with time and location. The abaxial surface of Rhapis excelsa and Cordyline fruticosa had fewer bacteria in contrast to its adaxial counterpart. This observation was consistent between noon and midnight and across five different locations. Our co-occurrence network analysis further showed that bacteria were found almost exclusively on the adaxial surface while only a small group of leaf blotch fungi thrived on the abaxial surface. There are higher densities of stomata on the abaxial surface and these openings are vulnerable ports of entry into the plant host. While one might argue about the settling of dust particles and microorganisms on the adaxial surface, we detected differences in reactive chemical activities and microstructures between the adaxial and abaxial surfaces. Our results further suggest that both plant species deploy different defence strategies to deter invading pathogens on the abaxial surface. We hypothesize that chemical and mechanical defence strategies evolved independently for harnessing and controlling phyllosphere microbiomes. Our findings have also advanced our understanding that the abaxial leaf surface is distinct from the adaxial surface and that the reduced microbial diversity is likely a consequence of plant-microbe interactions.

Objective: Interindividual variability in the clinical progression of COVID-19 may be explained by host genetics. Emerging literature supports a potential inherited predisposition to severe forms of COVID-19. Demographic and inflammatory characteristics of COVID-19 suggest that acquired hematologic mutations leading to clonal hematopoiesis (CH) may further increase vulnerability to adverse sequelae. This review summarizes the available literature examining genetic predispositions to severe COVID-19 and describes how these findings could eventually be used to improve its clinical management.Data Sources: A PubMed literature search was performed.Study Selection: Studies examining the significance of inherited genetic variation or acquired CH mutations in severe COVID-19 were selected for inclusion.Data Extraction: Relevant genetic association data and aspects of study design were qualitatively assessed and narratively synthesized.Data Synthesis: Genetic variants affecting inflammatory responses may increase susceptibility to severe COVID-19. Genome-wide association studies and candidate gene approaches have identified a list of inherited mutations, which likely alter cytokine and interferon secretion, and lung-specific mechanisms of immunity in COVID-19. The potential role of CH in COVID-19 is more uncertain at present; however, the available evidence suggests that the various types of acquired mutations and their differential influence on immune cell function must be carefully considered.Conclusions: The current literature supports the hypothesis that host genetic factors affect vulnerability to severe COVID-19. Further research is required to confirm the full scope of relevant variants and the causal mechanisms underlying these associations. Clinical approaches, which consider the genetic basis of interindividual variability in COVID-19 and potentially other causes of critical illness, could optimize hospital resource allocation, predict responsiveness to treatment, identify more efficacious drug targets, and ultimately improve outcomes.

Abstract Background Anthracosis is a disease generally considered to be in the lungs resulting from exposure to industrial dust in the workplace. Esophageal anthracosis is a fairly rare phenomenon and shows a strong correlation with tuberculosis. Moreover, esophageal involvement in tuberculosis is also rare. We here present an extremely rare case in which follow-up gastroesophageal endoscopy revealed a mass with a sunken, black area in the center and raised ring-like pattern in the surrounding mucosa resembling malignant melanoma. Uncovering the patient’s tuberculosis history finally avoided a misdiagnosis or overtreatment. Case presentation A 67-year-old male patient was admitted to the hospital due to “repeated chest pain for 1 month”. Endoscopic ultrasonography and contrast-enhanced CT scans revealed a mass adjacent to the esophageal wall with unclear boundaries. Aspiration biopsy confirmed that esophageal tuberculosis was caused by nearby mediastinal tuberculous lymphadenitis. After a standard anti-tuberculosis treatment regimen, the patient achieved a favorable prognosis. The follow-up gastroesophageal endoscopy showed a sunken black lesion with elevated peripheral mucosa replacing the original tuberculous mass, which was thought to be anthracosis, a disease that rarely occurs in the esophagus. Conclusion The diagnosis of tuberculosis should be taken into consideration when a submucosal mass appears in the middle part of the esophagus. Endoscopic ultrasonography can effectively contribute to a definite diagnosis. Moreover, this is the first case of esophageal anthracosis observed only 1 year after the treatment of tuberculosis, indicating esophageal anthracosis can be a short-term disease. The traction of the reduction of tubercular mediastinal lymph nodes after anti-tuberculosis treatment may create a circumstance for pigmentation or dust deposition. …

Abstract Background Healthcare-associated infections (HAIs) are a threat to patients. Accurate surveillance is required to identify and prevent HAIs. To estimate the incidence rate, report the accuracy and identify the barriers of reporting HAIs using a mixed-method study. Methods In this quantitative study, we externally evaluated the incidence rate and accuracy of the routine surveillance system in one of the main hospitals by an active follow-up of patients from September to December 2021. We used in-depth interviews with 18 experts to identify the barriers of the routine surveillance system. Results Among 404 hospitalized patients, 88 HAIs were detected. The estimated rate of HAIs was 17.1 (95% Confidence Intervals 95: 14.1, 21.1) per 1000 patient-days follow-up. However, in the same period, 116 HAIs were reported by the routine surveillance system, but the agreement between the two approaches was low (sensitivity = 61.4%, specificity = 82.6%, negative predictive value = 89.7%, and positive predictive validity = 46.5%). The minimum and maximum positive predictive values were observed in urinary tract infection (32.3%) and surgical site infection (60.9%). The main barrier of reporting HAIs was lack of cooperation in reporting HAIs by infection control link nurses and laboratory supervisors. Conclusions The discrepancy between the longitudinal study findings and the routine surveillance might be related to the inaccessibility of the surveillance system to clinical information of patients. In this regard, decreasing the barriers, increasing the knowledge of infection control nurses and other nurses, as well as the development of hospital information systems are necessary. …

Abstract Background Nasopharyngeal swabs are taken to determine the causative agent of community acquired pneumonia (CAP), while the reliability of upper respiratory tract sampling as a proxy for lower respiratory tract infections is still unclear. Methods Nasopharyngeal (NP) swabs, bronchoalveolar lavage (BAL) fluid samples and clinical data were collected from 153 hospitalized children between 3 months and 14 years of age with severe CAP, enrolled from March to June 2019. Written informed consent for the storage and use of the samples for further studies was obtained from the parents or caregivers. Putative pathogens were detected using a sensitive, high-throughput GeXP-based multiplex PCR and qPCR. Results The same bacterial species in paired samples were found in 29 (23.4%) and the same viral species in 52 (27.5%) of the patients. moderate concordance was found for Mycoplasma pneumoniae (ĸ=0.64), followed by Haemophilus influenzae (ĸ=0.42). The strongest discordance was observed for human adenovirus and also for Pseudomonas aeruginosa, the latter was exclusively detected in BAL samples. In the adenovirus cases strong concordance was associated with high viral loads in the NP swabs. Conclusion The variation in concordance in pathogen detection in the upper and lower respiratory tract of children with severe pneumonia is generally high but varies depending on the species. Novel and impactful insights are the concordance between NP and BAL detection for M. pneumoniae and H. influenzae and the strong correlation between high adenoviral loads in NP swabs and detection in BAL fluid. …

Abstract Background Malaria is endemic in 95% of Uganda and constitutes the country’s most significant public health problem—being the leading cause of morbidity and mortality, especially among children under five years of age. The current national malaria treatment policy is to use artemisinin-based combination therapy (ACT) as first-line treatment, and recommends parasitological confirmation of malaria before therapy. Adherence to this policy, however, remains suboptimal, with the self-initiated home-based therapy being common—posing undue exposures to, and pressure on the current artemisinin-based combinations, with the danger of emergence of drug resistance. The study evaluated the anti-malarial use and its appropriateness among febrile children under five presenting to a tertiary health facility in northern Uganda in light of the current malaria treatment policy. Methods This was a cross-sectional study in a tertiary health facility in northern Uganda between March and September 2021. Children aged 6–59 months with fever were selected using systematic random sampling. A pretested interviewer-administered questionnaire was used to collect clinical data from the caregivers. Data were analysed using SPSS version 23. Descriptive statistics and multiple logistic regression models were applied. P-value < 0.05 was considered for statistical significance. Results Seventy-two (34.3%) of the 210 children with fever in this study used anti-malarials prior to the hospital visit, 29.2% (21/72) of which were on a self-medication basis, 22.2% (16/72) were empiric prescriptions—all of which inappropriate, and only 48.6% (35/72) were prescribed based on a parasitological diagnosis of malaria. The most commonly used anti-malarials were artemether-lumefantrine 60/72 (88.3%), while a lesser proportion of quinine 7/72 (9.7%), artesunate 3/72 (4.2%) and dihydroartemisinin-piperaquine 2/72 (2.8%) were used. The factors independently associated with anti-malarial use among the children with febrile illnesses were duration of fever (p = 0.001); level of the nearest facility (p = 0.027), distance from the nearest health facility (p = 0.025), and caregivers’ age (p = 0.038). Conclusions Inappropriate use of anti-malarials for childhood febrile illnesses is prevalent in the study setting, facilitated by the ease of over-the-counter access, empiric prescription and use of leftover anti-malarials. This calls for a need to address communities’ health-seeking behaviour and the health providers’ practice alike. …

Abstract Background Anopheles stephensi is a malaria-transmitting mosquito that has recently expanded from its primary range in Asia and the Middle East, to locations in Africa. This species is a competent vector of both Plasmodium falciparum and Plasmodium vivax malaria. Perhaps most alarming, the characteristics of An. stephensi, such as container breeding and anthropophily, make it particularly adept at exploiting built environments in areas with no prior history of malaria risk. Methods In this paper, global maps of thermal transmission suitability and people at risk (PAR) for malaria transmission by An. stephensi were created, under current and future climate. Temperature-dependent transmission suitability thresholds derived from recently published species-specific thermal curves were used to threshold gridded, monthly mean temperatures under current and future climatic conditions. These temperature driven transmission models were coupled with gridded population data for 2020 and 2050, under climate-matched scenarios for future outcomes, to compare with baseline predictions for 2020 populations. Results Using the Global Burden of Disease regions approach revealed that heterogenous regional increases and decreases in risk did not mask the overall pattern of massive increases of PAR for malaria transmission suitability with An. stephensi presence. General patterns of poleward expansion for thermal suitability were seen for both P. falciparum and P. vivax transmission potential. Conclusions Understanding the potential suitability for An. stephensi transmission in a changing climate provides a key tool for planning, given an ongoing invasion and expansion of the vector. Anticipating the potential impact of onward expansion to transmission suitable areas, and the size of population at risk under future climate scenarios, and where they occur, can serve as a large-scale call for attention, planning, and monitoring. …

Tropical Medicine &International Health, Accepted Article.

Spondylodiscitis is an infection of vertebral body and intervertebral disc. It may be acquired by haematogenous spread of the pathogen from a distant site (most common route of infection), direct inoculation from trauma, invasive spinal diagnostic procedures or spinal surgery, or contiguous spread from adjacent soft tissue infection [1,2]. Most patients have mono-microbial infection, with Staphylococcus aureus being the most common etiological germ; other potential pathogens of spondylodiscitis include coagulase-negative staphylococci, streptococci, gram negative bacteria (such as Enterobacteriaceae and Pseudomonas aeruginosa), and rarely Mycobacterium tuberculosis and Brucella spp.

We propose a clinical trial evaluating the efficacy of piperacillin-tazobactam as compared to a carbapenem for the treatment of graft pyelonephritis caused by extended spectrum betalactamase (ESBL) producing Enterobacteriaceae.

Before the advent of anti-tuberculosis drugs in the 1940’s, tuberculous meningitis (TBM) was a much feared and almost universally fatal form of tuberculosis. Thus when the first anti-tuberculosis drugs, streptomycin and para-aminosalycilic acid (PAS), became available, they were given first to those with TBM. Suddenly, the disease became treatable. Case-fatality fell from 70% with streptomycin and PAS, to around 30% with the combination of isoniazid, pyrazinamide and rifampicin[1].

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Proceedings of the National Academy of Sciences, Volume 120, Issue 13, March 2023.

AbstractPower-to-X (P2X) technologies will play a more important role in the conversion of electric power to storable energy carriers, commodity chemicals and even food and feed. Among the different P2X technologies, microbial components form cornerstones of individual process steps. This review comprehensively presents the state-of-the-art of different P2X technologies from a microbiological standpoint. We are focusing on microbial conversions of hydrogen from water electrolysis to methane, other chemicals and proteins. We present the microbial toolbox needed to gain access to these products of interest, assess its current status and research needs, and discuss potential future developments that are needed to turn todays P2X concepts into tomorrow's technologies.

AbstractTerpenoids, also known as isoprenoids, are the largest and most diverse class of organic compounds in nature and are involved in many membrane-associated cellular processes, including membrane organization, electron transport chain, cell signaling, and phototrophy. Terpenoids are ancient compounds with their origin presumably before the last universal common ancestor. However, Bacteria and Archaea are known to possess two distinct terpenoid repertoires and utilize terpenoids differently. Most notably, Archaea constitute their cellular membrane solely made of terpenoid-based phospholipids, contrary to the bacterial membrane that consists of fatty acid-based phospholipids. Thus, the composition of ancestral membranes at the beginning of cellular life and the diversification of terpenoids in early life remain enigmatic. This review addresses these key issues through comprehensive phylogenomic analyses of extant terpenoid biosynthesis enzymes in Bacteria and Archaea. We aim to infer the basal components of terpenoid biosynthesis machinery that have an ancient origin before the divergence of the two domains and shed light on the deep evolutionary connection between terpenoid biochemistry and early life.

AbstractBackgroundLung transplantation is one of the only options for patients with severe COVID-19-associated lung injury (CALI). Studies on patients who received a lung transplant for CALI have, to date, not looked at the infectious outcomes.MethodsAfter IRB approval, a retrospective case-control cohort study, matched 1:1, collected data on patients who underwent lung transplantation for CALI (case) and for non-COVID-19 end-stage lung disease (control) between June 1, 2020 and April 1, 2022 at a large academic hospital in Chicago. We assessed infectious complications and other key outcomes pre-transplant and for one-year post-transplant.ResultsAmong 78 subjects (39 CALI and 39 matched control lung transplant patients), those in the CALI cohort were less likely to be vaccinated pre-transplant and were more likely to have diabetes, obesity, to not be ambulatory and to require pre-transplant ECMO and mechanical ventilation. Patients transplanted for CALI had higher rates of infection pre-transplant (66.7% vs 15.4% of patients in the control) and in the first 30 days post-transplant (43.6% vs. 20.5%). Numbers and types of infection were similar in both groups at other time points. One year mortality was similar (12.8% vs. 10.3%) for CALI and control populations, respectively.ConclusionsPatients who received a lung transplant for CALI are more deconditioned with prolonged hospital stays and experience more infectious complications immediately pre- and post-transplant. Infections due to MDROs are important contributors to morbidity and mortality in this population and antimicrobial stewardship is urgently needed.

AbstractBackgroundOlder adults are recommended to receive influenza vaccination annually and many use statins. Statins have immunomodulatory properties that might modify influenza vaccine effectiveness (VE) and alter influenza infection risk.MethodsUsing the test-negative design and linked laboratory and health administrative databases in Ontario, Canada, we estimated VE against laboratory-confirmed influenza among community-dwelling statin users and non-users aged ≥66 years during the 2010-2011 to 2018-2019 influenza seasons. We also estimated the odds ratio (OR) for influenza infection between statin users and non-users by vaccination status.ResultsAmong subjects tested for influenza across the 9 seasons, 54,243 had continuous statin exposure prior to testing and 48,469 were deemed unexposed. VE against laboratory-confirmed influenza was similar between statin users and non-users (17% [95%CI, 13-20%] and 17% [95%CI, 13-21%] respectively; test for interaction, p=0.87). In both vaccinated and unvaccinated subjects, statin users had higher odds of laboratory-confirmed influenza than non-users (OR for vaccinated =1.15; 95%CI, 1.10-1.21; OR for unvaccinated=1.15; 95%CI, 1.10-1.20). These findings were consistent by mean daily dose and statin type. VE did not differ between users and non-users of other cardiovascular drugs, except for beta-blockers. We did not observe that vaccinated and unvaccinated users of these drugs had increased odds of influenza, except for unvaccinated beta-blocker users.ConclusionsInfluenza VE did not differ between statin users and non-users. Statin use was associated with increased odds of laboratory-confirmed influenza in vaccinated and unvaccinated subjects, but these associations might be impacted by residual confounding.

An error appeared in the corrected proof publication of this article (Tong et al. “The Staphylococcus aureus Network Adaptive Platform Trial Protocol: New Tools for an Old Foe.” Clin Infect Dis; https://doi.org/10.1093/cid/ciac476). The list of members of the Staphylococcus aureus Network Adaptive Platform (SNAP) Study Group was incomplete. An amended list of study group members appears below; names of collaborators who were initially left off the list appear in bold. Additionally, two researchers initially included in the study group, Kevin Brown and Nan Vasilunas, have been removed from the list of contributors.

ObjectivesTo explore the acceptability of regular asymptomatic testing for SARS-CoV-2 on a university campus using saliva sampling for PCR analysis and the barriers and facilitators to participation.DesignCross-sectional surveys and qualitative semistructured interviews.SettingEdinburgh, Scotland.ParticipantsUniversity staff and students who had registered for the testing programme (TestEd) and provided at least one sample.Results522 participants completed a pilot survey in April 2021 and 1750 completed the main survey (November 2021). 48 staff and students who consented to be contacted for interview took part in the qualitative research. Participants were positive about their experience with TestEd with 94% describing it as ‘excellent’ or ‘good’. Facilitators to participation included multiple testing sites on campus, ease of providing saliva samples compared with nasopharyngeal swabs, perceived accuracy compared with lateral flow devices (LFDs) and reassurance of test availability while working or studying on campus. Barriers included concerns about privacy while testing, time to and methods of receiving results compared with LFDs and concerns about insufficient uptake in the university community. There was little evidence that the availability of testing on campus changed the behaviour of participants during a period when COVID-19 restrictions were in place.ConclusionsThe provision of free asymptomatic testing for COVID-19 on a university campus was welcomed by participants and the use of saliva-based PCR testing was regarded as more comfortable and accurate than LFDs. Convenience is a key facilitator of participation in regular asymptomatic testing programmes. Availability of testing did not appear to undermine engagement with public health guidelines.…

ObjectivesThis study aims to compare the clinical manifestations, laboratory findings, outcomes and overall survival time of patients with COVID-19 with and without comorbidities.DesignRetrospective design.SettingThis study was undertaken at two hospitals in Damascus.ParticipantsA total of 515 Syrian patients met the inclusion criterion, laboratory-confirmed COVID-19 infection following the Centers for Disease Control and Prevention. Exclusion criteria were suspected and probable cases that were not confirmed with a positive reverse transcription-PCR assay, and patients who self-discharged from the hospital against medical advice.Primary and secondary outcome measuresFirst, assess the impacts of comorbidities on COVID-19 infection in four areas (clinical manifestations, laboratory findings, severity and outcomes). Second, calculate the overall survival time for patients with COVID-19 with comorbidities.ResultsOf 515 patients included, 316 (61.4%) were male and 347 (67.4%) had at least one coexisting chronic disease. Patients with comorbidities compared with no comorbidities were more vulnerable to poor outcomes such as severe infection (32.0% vs 9.5%, p<0.001), severe complications (34.6% vs 9.5%, p<0.001), the need for mechanical ventilation (28.8% vs 7.7%, p<0.001) and death (32.0% vs 8.3%, p<0.001). Multiple logistic regression showed that age ≥65 years old, positive smoking history, having ≥2 comorbidities and chronic obstructive pulmonary disease were risk factors linked to severe COVID-19 infection in patients with comorbidities. Overall survival time was lower among patients with comorbidities (vs no comorbidities), patients with ≥2 comorbidities (vs one comorbidity), and patients with hypertension, chronic obstructive pulmonary disease, malignancy or obesity (vs other comorbidities) (p<0.05).ConclusionThis study revealed that COVID-19 infection had poor outcomes among those with comorbidities. Severe complications, mechanical ventilation usage and death were more prevalent among patients with comorbidities compared with those with no comorbidities.…

IntroductionCancer diagnosis and treatment can impair fertility, and younger female patients with cancer have a particularly strong need for fertility preservation. Fertility preservation decision aids are thought to help patients make proactive and informed treatment decisions. This systematic review aims to assess the effectiveness and feasibility of online fertility preservation decision aids for young female patients with cancer.Methods and analysisPubMed, Web of Science Core Collection, Embase, The Cochrane Central Register of Controlled Trials, PsycINFO and CHINAL, along with three grey literature sources (Google Scholar, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform), will be searched from each database’s establishment to 30 November 2022. Two trained reviewers will independently screen the articles, and the data extraction and methodological quality of eligible randomised controlled trials and quasiexperimental studies will be assessed. A meta-analysis will be performed using Review Manager V.5.4 (Cochrane Collaboration) software, and heterogeneity will be assessed using I² statistics. If a meta-analysis is not possible, a narrative synthesis will be done.Ethics and disseminationSince this systematic review is based on published data, no ethical approval is required. The study’s findings will be disseminated through peer-reviewed publications and conference presentations.PROSPERO registration numberCRD42022363287.…

by Samiha Benrabaa, Ian Orchard, Angela B. LangeEcdysteroids control ovary growth and egg production through a complex gene hierarchy. In the female Rhodnius prolixus, a blood-gorging triatomine and the vector of Chagas disease, we have identified the ecdysone response genes in the ovary using transcriptomic data. We then quantified the expression of the ecdysone response gene transcripts (E75, E74, BR-C, HR3, HR4, and FTZ-F1) in several tissues, including the ovary, following a blood meal. These results confirm the presence of these transcripts in several tissues in R. prolixus and show that the ecdysone response genes in the ovary are mostly upregulated during the first three days post blood meal (PBM). Knockdown of E75, E74, or FTZ-F1 transcripts using RNA interference (RNAi) was used to understand the role of the ecdysone response genes in vitellogenesis and egg production. Knockdown significantly decreases the expression of the transcripts for the ecdysone receptor and Halloween genes in the fat body and the ovaries and reduces the titer of ecdysteroid in the hemolymph. Knockdown of each of these transcription factors typically alters the expression of the other transcription factors. Knockdown also significantly decreases the expression of vitellogenin transcripts, Vg1 and Vg2, in the fat body and ovaries and reduces the number of eggs produced and laid. Some of the laid eggs have an irregular shape and smaller volume, and their hatching rate is decreased. Knockdown also influences the expression of the chorion gene transcripts Rp30 and Rp45. The overall effect of knockdown is a decrease in number of eggs produced and a severe reduction in number of eggs laid and their hatching rate. Clearly, ecdysteroids and ecdysone response genes play a significant role in reproduction in R. prolixus.

by Vulstan James Shedura, Ally Kassim Hussein, Salum Kassim Nyanga, Doreen Kamori, Geofrey Joseph MchauBackground The World Health Organization (WHO) recommends periodic evaluations of influenza surveillance systems to identify areas for improvement and provide evidence of data reliability for policymaking. However, data on the performance of established influenza surveillance systems are limited in Africa, including Tanzania. We aimed to assess the usefulness of the Influenza surveillance system in Tanzania and to ascertain if the system meets its objectives, including; estimating the burden of disease caused by the Influenza virus in Tanzania and identifying any circulating viral strains with pandemic potential. Methodology From March to April 2021, we collected retrospective data through a review of the Tanzania National Influenza Surveillance System electronic forms for 2019. Furthermore, we interviewed the surveillance personnel about the system’s description and operating procedures. Case definition (ILI-Influenza Like Illness and SARI-Severe Acute Respiratory Illness), results, and demographic characteristics of each patient were obtained from the Laboratory Information System (Disa*Lab) at Tanzania National Influenza Center. The United States Centers for disease control and prevention updated guidelines for evaluating public health surveillance systems were used to evaluate the system’s attributes. Additionally, the system’s performance indicators (including turnaround time) were obtained by evaluating Surveillance system attributes, each being scored on a scale of 1 to 5 (very poor to excellent performance). Results A total of 1731 nasopharyngeal and oropharyngeal samples were collected from each suspected influenza case in 2019 from fourteen (14/14) sentinel sites of the influenza surveillance system in Tanzania. Laboratory-confirmed cases were 21.5% (373/1731) with a predictive value positive of 21.7%. The majority of patients (76.1%) tested positive for Influenza A. Thirty-seven percent of patients’ results met the required turnaround time, and 40% of case-based forms were incompletely filled. Although the accuracy of the data was good (100%), the consistency of the data was below (77%) the established target of ≥ 95%. Conclusion The overall system performance was satisfactory in conforming with its objectives and generating accurate data, with an average performance of 100%. The system’s complexity contributed to the reduced consistency of data from sentinel sites to the National Public Health Laboratory of Tanzania. Improvement in the use of the available data could be made to inform and promote preventive measures, especially among the most vulnerable population. Increasing sentinel sites would increase population coverage and the level of system representativeness.…

by Linda Carman Copel, Suzanne C. Smeltzer, Christine D. Byrne, Mu-Hsun Chen, Donna S. Havens, Peter Kaufmann, Heather Brom, Jennifer Dean Durning, Linda Maldonado, Patricia K. Bradley, Janell Mensinger, Jennifer YostAims and objectives Studies have shown that the COVID-19 pandemic has taken a toll on individuals who interact with patients with SARS-CoV-2 but focused largely on clinicians in acute care settings. This qualitative descriptive study aimed to understand the experiences and well-being of essential workers across settings during the pandemic. Background Multiple studies of the well-being of individuals who have cared for patients during the pandemic have included interviews of clinicians from acute care settings and revealed high levels of stress. However, other essential workers have not been included in most of those studies, yet they may also experience stress. Methods Individuals who participated in an online study of anxiety, depression, traumatic distress, and insomnia, were invited to provide a free-text comment if they had anything to add. A total of 2,762 essential workers (e.g., nurses, physicians, chaplains, respiratory therapists, emergency medical technicians, housekeeping, and food service staff, etc.) participated in the study with 1,079 (39%) providing text responses. Thematic analysis was used to analyze those responses. Results Four themes with eight sub-themes were: Facing hopelessness, yet looking for hope; Witnessing frequent death; Experiencing disillusionment and disruption within the healthcare system, and Escalating emotional and physical health problems. Conclusions The study revealed major psychological and physical stress among essential workers. Understanding highly stressful experiences during the pandemic is essential to identify strategies that ameliorate stress and prevent its negative consequences. This study adds to the research on the psychological and physical impact of the pandemic on workers, including non-clinical support personnel often overlooked as experiencing major negative effects. Relevance to clinical practice The magnitude of stress among all levels of essential workers suggests the need to develop strategies to prevent or alleviate stress across disciplines and all categories of workers.…

by Yi-Tseng Tsai, Sriyani Padmalatha K. M., Han-Chang Ku, Yi-Lin Wu, Nai-Ying KoDeath by suicide is a major public health problem. People living with human immunodeficiency virus (PLHIV) have higher risk of suicidal behavior than the general population. The aim of this review is to summarize suicidal behavior, associated risk factors, and risk populations among PLHIV. Research studies in six databases from January 1, 1988, to July 8, 2021, were searched using keywords that included “HIV,” “suicide,” and “risk factors.” The study design, suicide measurement techniques, risk factors, and study findings were extracted. A total of 193 studies were included. We found that the Americas, Europe, and Asia have the highest rates of suicidal behavior. Suicide risk factors include demographic factors, mental illness, and physiological, psychological, and social support. Depression is the most common risk factor for PLHIV, with suicidal ideation and attempt risk. Drug overdosage is the main cause of suicide death. In conclusion, the current study found that PLHIV had experienced a high level of suicidal status. This review provides an overview of suicidal behavior and its risk factors in PLHIV with the goal of better managing these factors and thus preventing death due to suicide.

by Callam T. Davidson, Eileen Miller, Morwenna Muir, John C. Dawson, Martin Lee, Stuart Aitken, Alan Serrels, Scott P. Webster, Natalie Z. M. Homer, Ruth Andrew, Valerie G. Brunton, Patrick W. F. Hadoke, Brian R. WalkerGlucocorticoids inhibit angiogenesis by activating the glucocorticoid receptor. Inhibition of the glucocorticoid-activating enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) reduces tissue-specific glucocorticoid action and promotes angiogenesis in murine models of myocardial infarction. Angiogenesis is important in the growth of some solid tumours. This study used murine models of squamous cell carcinoma (SCC) and pancreatic ductal adenocarcinoma (PDAC) to test the hypothesis that 11β-HSD1 inhibition promotes angiogenesis and subsequent tumour growth. SCC or PDAC cells were injected into female FVB/N or C57BL6/J mice fed either standard diet, or diet containing the 11β-HSD1 inhibitor UE2316. SCC tumours grew more rapidly in UE2316-treated mice, reaching a larger (P…

Abstract Background Nasopharyngeal swabs are taken to determine the causative agent of community acquired pneumonia (CAP), while the reliability of upper respiratory tract sampling as a proxy for lower respiratory tract infections is still unclear. Methods Nasopharyngeal (NP) swabs, bronchoalveolar lavage (BAL) fluid samples and clinical data were collected from 153 hospitalized children between 3 months and 14 years of age with severe CAP, enrolled from March to June 2019. Written informed consent for the storage and use of the samples for further studies was obtained from the parents or caregivers. Putative pathogens were detected using a sensitive, high-throughput GeXP-based multiplex PCR and qPCR. Results The same bacterial species in paired samples were found in 29 (23.4%) and the same viral species in 52 (27.5%) of the patients. moderate concordance was found for Mycoplasma pneumoniae (ĸ=0.64), followed by Haemophilus influenzae (ĸ=0.42). The strongest discordance was observed for human adenovirus and also for Pseudomonas aeruginosa, the latter was exclusively detected in BAL samples. In the adenovirus cases strong concordance was associated with high viral loads in the NP swabs. Conclusion The variation in concordance in pathogen detection in the upper and lower respiratory tract of children with severe pneumonia is generally high but varies depending on the species. Novel and impactful insights are the concordance between NP and BAL detection for M. pneumoniae and H. influenzae and the strong correlation between high adenoviral loads in NP swabs and detection in BAL fluid. …

Abstract Background Understanding Plasmodium falciparum population diversity and transmission dynamics provides information on the intensity of malaria transmission, which is needed for assessing malaria control interventions. This study aimed to determine P. falciparum allelic diversity and multiplicity of infection (MOI) among asymptomatic and symptomatic school-age children in Kinshasa Province, Democratic Republic of Congo (DRC). Methods A total of 438 DNA samples (248 asymptomatic and 190 symptomatic) were characterized by nested PCR and genotyping the polymorphic regions of pfmsp1 block 2 and pfmsp2 block 3. Results Nine allele types were observed in pfmsp1 block2. The K1-type allele was predominant with 78% (229/293) prevalence, followed by the MAD20-type allele (52%, 152/293) and RO33-type allele (44%, 129/293). Twelve alleles were detected in pfmsp2, and the 3D7-type allele was the most frequent with 84% (256/304) prevalence, followed by the FC27-type allele (66%, 201/304). Polyclonal infections were detected in 63% (95% CI 56, 69) of the samples, and the MOI (SD) was 1.99 (0.97) in P. falciparum single-species infections. MOIs significantly increased in P. falciparum isolates from symptomatic parasite carriers compared with asymptomatic carriers (2.24 versus 1.69, adjusted b: 0.36, (95% CI 0.01, 0.72), p = 0.046) and parasitaemia > 10,000 parasites/µL compared to parasitaemia < 5000 parasites/µL (2.68 versus 1.63, adjusted b: 0.89, (95% CI 0.46, 1.25), p < 0.001). Conclusion This survey showed low allelic diversity and MOI of P. falciparum, which reflects a moderate intensity of malaria transmission in the study areas. MOIs were more likely to be common in symptomatic infections and increased with the parasitaemia level. Further studies in different transmission zones are needed to understand the epidemiology and parasite complexity in the DRC. …

Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

Infection and Immunity, Ahead of Print.

The emergence of SARS-CoV-2 causing the prolonged COVID-19 pandemic has had profound public health and socio-economic consequences worldwide [1]. Throughout the course of the pandemic, the rapid mutation of SARS-CoV-2 has spawned numerous novel strains including variants of concern (VOCs) – further complicating infection control measures with altered transmissibility, virulence, and immune evasion [2,3]. Currently, the world is gradually transitioning to endemicity with the rapid spread and dominance of the Omicron VOC and its subvariants.

Peritonitis is a common complication of peritoneal dialysis (PD), which is significantly related to the mortality of PD patients [1]. Mycoplasma hominis, Ureaplasma parvum, and Ureaplasma urealyticum commonly colonize the urogenital tract [2]. PD-associated peritonitis caused by them has rarely been reported. Herein, we reported four cases of this disease and reviewed the literature.