Assessment and clinical utility of metagenomic next-generation sequencing for suspected lower respiratory tract infections.

OBJECTIVES: This study aims to compare the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) to traditional diagnostic methods in patients with lower respiratory tract infections (LRTIs), elucidate the etiological spectrum of these infections, and explore the impact of mNGS on guiding antimicrobial therapy. METHODS: We retrospectively analyzed data from 128 patients admitted to the Respiratory Department of Anqing 116 Hospital between July 2022 and July 2023. All patients had undergone both mNGS and conventional microbiological techniques (CMT) for LRTI diagnosis. We assessed the diagnostic performance of these methods and examined the influence of mNGS on antimicrobial decision-making. RESULTS: Overall, mNGS demonstrated superior sensitivity (96.8%) and accuracy (96.8%) compared to CMT. For Mycobacterium tuberculosis detection, the accuracy and sensitivity of mNGS was 88.8% and 77.6%, which was lower than the 94.7% sensitivity of the T-spot test and the 79.6% sensitivity of CMT. In fungal pathogen detection, mNGS showed excellent sensitivity (90.5%), specificity (86.7%), and accuracy (88.0%). Bacteria were the predominant pathogens detected (75.34%), with Mycobacterium tuberculosis (41.74%), Streptococcus pneumoniae (21.74%), and Haemophilus influenzae (16.52%) being most prevalent. Bacterial infections were most common (62.10%), followed by fungal and mixed infections (17.74%). Of the 118 patients whose treatment regimens were adjusted based on mNGS results, 102 (86.5%) improved, 7 (5.9%) did not respond favorably, and follow-up was lost for 9 patients (7.6%). CONCLUSIONS: mNGS offers rapid and precise pathogen detection for patients with suspected LRTIs and shows considerable promise in diagnosing Mycobacterium tuberculosis and fungal infections. By broadening the pathogen spectrum and identifying polymicrobial infections, mNGS can significantly inform and refine antibiotic therapy.

Clusters of heterogeneity of tuberculosis-HIV coinfection in Brazil: a geospatial study.

OBJECTIVE: To analyze the geospatialization of tuberculosis-HIV coinfection in Brazil, from 2010 to 2021, and the correlation with socioeconomic, housing, and health indicators. METHODS: An ecological study of Brazilian municipalities and states, with data from HIV and tuberculosis information systems, previously reported by the Ministry of Health. The crude and smoothed coefficients were calculated by the local empirical Bayesian method of incidence of coinfection per 100,000 inhabitants in the population aged between 18 and 59 years. Univariate (identification of clusters) and bivariate (correlation with 20 indicators) Moran's indices were used. RESULTS: A total of 122,223 cases of coinfection were registered in Brazil from 2010 to 2021, with a mean coefficient of 8.30/100,000. The South (11.44/100,000) and North (9.93/100,000) regions concentrated the highest burden of infections. The coefficients dropped in Brazil, in all regions, in the years of covid-19 (2020 and 2021). The highest coefficients were observed in the municipalities of the states of Rio Grande do Sul, Mato Grosso do Sul, and Amazonas, with high-high clusters in the capitals, border regions, coast of the country. The municipalities belonging to the states of Minas Gerais, Bahia, Paraná, and Piauí showed low-low clusters. There was a direct correlation with human development indices and aids rates, as well as an indirect correlation with the proportion of poor or of those vulnerable to poverty and the Gini index. CONCLUSIONS: The spatial analysis of tuberculosis-HIV coinfection showed heterogeneity in the Brazilian territory and constant behavior throughout the period, revealing clusters with high-burden municipalities, especially in large urban centers and in states with a high occurrence of HIV and/or tuberculosis. These findings, in addition to alerting to the effects of the covid-19 pandemic, can incorporate strategic planning for the control of coinfection, aiming to eliminate these infections as public health problems by 2030.

Assessment of Culicidae collection methods for xenomonitoring lymphatic filariasis in malaria co-infection context in Burkina Faso.

BACKGROUND: Entomological surveillance of lymphatic filariasis and malaria infections play an important role in the decision-making of national programs to control, or eliminate these both diseases. In areas where both diseases prevalence is low, a large number of mosquitoes need to be sampled to determine vectors infection rate. To do this, efficient mosquito collection methods must be used. This study is part in this framework, to assess appropriate mosquito collection methods for lymphatic filariasis xenomonitoring in a coexistence context with malaria in Burkina Faso. METHODOLOGY/PRINCIPAL FINDINGS: Mosquito collections were performed between August and September 2018 in four villages (Koulpissi, Seiga, and Péribgan, Saptan), distributed in East and South-West health regions of Burkina Faso. Different collection methods were used: Human Landing Catches (HLC) executed indoor and outdoor, Window Exit-Trap, Double Net Trap (DNT) and Pyrethrum Spray Catches (PSC). Molecular analyses were performed to identify Anopheles gambiae s.l. sibling species and to detect Wuchereria bancrofti and Plasmodium falciparum infection in Anopheles mosquitoes. A total of 3 322 mosquitoes were collected among this, Anopheles gambiae s.l. was the vector caught in largest proportion (63.82%). An. gambiae s.l. sibling species molecular characterization showed that An. gambiae was the dominant specie in all villages. The Human Landing Catches (indoor and outdoor) collected the highest proportion of mosquitoes (between 61.5% and 82.79%). For the sampling vectors infected to W. bancrofti or P. falciparum, PSC, HLC and Window Exit-Trap were found the most effective collection methods. CONCLUSIONS/SIGNIFICANCE: This study revealed that HLC indoor and outdoor remained the most effective collection method. Likewise, the results showed the probability to use Window Exit-Trap and PSC collection methods to sample Anopheles infected.

A Functional Assessment of Fetal Liver and Monocyte-Derived Macrophages in the Lung Alveolar Environment.

It is becoming clear that every organ is seeded by a population of fetal liver-derived macrophages that are replaced at different rates by monocyte-derived macrophages. Using the Ms4a3tdTomato reporter mouse that reports on monocyte-derived alveolar macrophages (Mo-AMs) and our ability to examine AM function using our multichannel intravital microscopy, we examined the fetal-liver derived alveolar macrophage (FL-AM) and Mo-AM populations within the same mouse under various environmental conditions. The experiments unveiled that AMs migrated from alveolus to alveolus and phagocytosed bacteria identically regardless of ontogenic origin. Using 50 PFU of influenza A virus (IAV) determined using the Madin-Darby canine kidney (MDCK) cell line, we noted that both populations were susceptible to IAV-induced immunoparalysis, which also led to impaired phagocytosis of secondary bacterial infections. Both FL-AMs and Mo-AMs were trained by ß-glucan to resist IAV-induced paralysis. Over time (40 wk), Mo-AMs began to outperform FL-AMs, although both populations were still sensitive to IAV. Our data also show that clodronate depletion of AMs leads to replenishment, but by FL-AMs, and these macrophages do show some functional impairment for a limited time. Overall, the system is designed such that new macrophages rapidly assume the function of tissue-resident macrophages when both populations are examined in an identical environment. These data do differ from artificial depletion methods that compare Mo-AMs and FL-AMs.

Analysis of Health-Related Quality of Life and Incurred Costs Among Human Immunodeficiency Virus, Tuberculosis, and Tuberculosis/HIV Coinfected Outpatients in Indonesia.

OBJECTIVES: A growing interest in healthcare costs and patients' health-related quality of life (HRQoL) exists in the context of the increasing importance of health technology assessment in countries with high numbers of the HIV and tuberculosis (TB) patient populations, such as Indonesia. This study aimed to analyze the HRQoL and out-of-pocket (OOP) costs of HIV, TB, and TB/HIV coinfected participants in a city in Indonesia with a high prevalence of HIV and TB. METHODS: A cross-sectional survey was conducted in the voluntary counseling and testing and lung clinics of Bekasi City Public Hospital (Indonesia) from January to March 2018. Patients' HRQoL was measured using the EQ-5D-5L questionnaire, whereas OOP costs were extracted from a semistructured questionnaire. RESULTS: Of the 460 eligible participants, 82% resided in the city, 48% of them were married, and their median age was 34 years. Less than half were insured, and more than half had no source of income. The median values of health utilities for participants with HIV, TB, and TB/HIV were perceived as potentially high (1.0, 0.9, and 0.8, respectively). The TB/HIV coinfected outpatients had the highest OOP costs (US$94.5), with the largest contribution coming from direct medical OOP expenditures. Taking loans from family members was adopted as a financial strategy to overcome inadequate household incomes and high treatment costs. CONCLUSION: This study suggests that TB/HIV coinfection potentially lowers HRQoL and increases healthcare costs and the need for economic analysis to underpin cost-effective treatment in such patients.

Semi-quantitative assessment of gastrointestinal viruses in stool samples with Seegene Allplex gastrointestinal panel assays: a solution to the interpretation problem of multiple pathogen detection?

PURPOSE: The aim of the study was to determine and evaluate the clinical usefulness of pathogen specific semi-quantitative cut-offs in stool samples with multiple pathogen detections. METHODS: The PCR (Seegene Allplex Gastrointestinal Virus Assay) data from 4527 positive samples received over 16 months were retrospectively analyzed to investigate the distribution of the Ct values of each individual viral pathogen. By using interquartile ranges for each viral pathogen, pathogen specific semi-quantitative cut-offs were determined. RESULTS: After a thorough analysis of the Ct values, a well-founded decision to exclude all results with a Ct value higher than 35 was made. This approach made it possible to generate a more nuanced report and to facilitate clinical interpretation in case of mixed infections by linking a lower Ct value of a pathogen to a greater likelihood of being a relevant causative pathogen. Moreover, not reporting viral pathogens with a Ct value higher than 35 led to a significant reduction (p < 0.0001) of reported mixed infections compared to oversimplified qualitative or qualitative reporting. CONCLUSION: By omitting very high Ct values and reporting semi-quantitatively, value was added to the syndromic reports, leading to an easier to read lab report, especially in mixed infections.

Transcriptome analysis revealed immune responses in the kidney of Atlantic salmon (Salmo salar) co-infected with sea lice (Lepeophtheirus salmonis) and infectious salmon anemia virus.

Sea lice (Lepeophtheirus salmonis) and infectious salmon anemia virus (ISAv) are two of the most important pathogens in Atlantic salmon (Salmo salar) farming and typically cause substantial economic losses to the industry. However, the immune interactions between hosts and these pathogens are still unclear, especially in the scenario of co-infection. In this study, we artificially infected Atlantic salmon with sea lice and ISAv, and investigated the gene expression patterns of Atlantic salmon head kidneys in response to both lice only and co-infection with lice and ISAv by transcriptomic analysis. The challenge experiment indicated that co-infection resulted in a cumulative mortality rate of 47.8 %, while no mortality was observed in the lice alone infection. We identified 240 differentially expressed genes (DEGs) under the lice alone infection, of which 185 were down-regulated and 55 were up-regulated, while a total of 994 DEGs were identified in the co-infection, of which 206 were down-regulated and 788 were significantly up-regulated. The pathway enrichment analysis revealed that single-infection significantly suppressed the innate immune system (e.g., the complement system), whereas co-infection induced a strong immune response, leading to the activation of immune-related signaling pathways such as Toll-like receptors and NOD-like receptors pathways, as well as significant upregulation of genes related to the activation of interferon and MH class I protein complex. Our results provide the first global transcriptomic study of gene expression in the Atlantic salmon head kidney in response to co-infection with sea lice and ISAv, and provided the baseline knowledge for understanding the immune responses during co-infection.

Characterization of respiratory bacterial co-infection and assessment of empirical antibiotic treatment in patients with COVID-19 at hospital admission.

Accurate characterization of respiratory bacterial co-infection is critical for guiding empirical antibiotic treatment for hospitalised patients with coronavirus disease 2019 (COVID-19). We retrospectively assessed the clinical and analytical predictors of respiratory bacterial co-infection and described the empirical use of antibiotics in COVID-19 hospitalised patients. Respiratory bacterial co-infection was documented in 6.9% (80/1157) of the patients. The predominant bacteria isolates were Haemophilus influenzae, followed by Streptococcus pneumoniae and Pseudomonas aeruginosa. Respiratory bacterial co-infection was associated with having had a positive culture for a respiratory pathogen in the last year (OR = 25.89), dyslipidaemia (OR = 2.52), heart failure (OR = 7.68), ferritin levels < 402 ng/mL (OR = 2.28), leukocyte count > 8.7 × 109/L (OR = 2.4), and patients with chronic obstructive pulmonary disease treated with inhaled corticosteroids (OR = 12.94). Empirical antibiotic treatment was administered in 42.33% of patients, although it declined across the distinct study periods (p < 0.001). Patients admitted to intensive care units harbouring co-infection exhibited worse outcomes and more bacterial secondary infections. In conclusion, respiratory bacterial co-infection prevalence was low, although it could lead to unfavourable outcomes. Moreover, the percentage of empirical antibiotic treatment remained high. The study's findings allowed the identification of several predictors for respiratory bacterial co-infection and could help implement adequate antibiotic stewardship measures.

What Is the Real Epidemiology of Hepatitis D Virus and Why so Many Mixed Messages?

The disease burden of HDV is poorly understood. Our review identified multiple reasons: (1) HDV infection rates are overestimated in the general population due to limited sample sizes, sampling high-risk populations, and significant regional variations, (2) estimates are based on chronic HBV populations, but HBV burden itself is uncertain, (3) there is a lack of testing in at-risk populations, (4) prevalence testing is based on HDV antibody testing and not HDV RNA, which distinguishes between active infection versus prior exposure, (5) older studies used less reliable testing and (6) HBV vaccination programs have affected HDV prevalence, but is often not accounted for.

Assessment of Fasciola and Paramphistomes co-infection in large ruminants through faecal egg counts around Taiping, Malaysia.

Emerging cases of Fasciola and Paramphistomes co-infection have been reported, especially in tropical regions. Thisis due to Fasciola and Paramphistomes sharing biological factors which influence the pattern of transmission, especially in faecal egg shedding due to interaction and competition in the definitive host. Most reports surveyed the occurrence of fasciolosis in ruminants with a lack of observation of faecal egg distribution. Therefore, present study is aimed to assess the distribution of Fasciola and Paramphistomes faecal egg count (fec) in co-infected large ruminants in Larut, Matang, and Selama areas (Taiping). A total of 371 faecal samples were collected at random from 23 ruminant herds. Flukefinder® sedimentation was used to quantify the Fasciola and Paramphistomes eggs. Descriptive analyses were performed to determine the prevalence of co-infections, and Spearman correlation analysis was used to correlate the fec. Overall, the prevalence of Fasciola and Paramphistomes co-infection was 23.7% (n=89/371) in Taiping. Prevalence of paramphistomosis was always higher than fasciolosis in overall and single infection, with 46.9% (n=174/371) and 22.9% (n=85/371) compared to 36.9% (n=137/371) and 12.9% (n=48/371) respectively. Egg per gram (epg) of both parasites were positively skewed with a median of 1.5 epg in fasciolosis and 10.5 epg in paramphistomosis. Spearman correlation analysis of the epg in co-infected bovine was found to have a moderately positive correlation with rs=0.39 (p-value<0.01). The recent study observed a moderate prevalence of Fasciola and Paramphistomes coinfection in a large ruminant population from Taiping, with the prevalence of paramphistomosis being higher than fasciolosis. Hence, this suggests that infection with one of these parasites increases the chance of infection with another. There is a need to integrate fec in parasite surveillance to monitor the trend of parasite transmission. Findings in the present study could tailor control strategies, especially for fasciolosis to limit the economic loss and prevent zoonotic transmission.

Assessment of co-infection with BNYVV and BSCTV on resistance against Rhizomania disease in transgenic sugar beet plants.

Sugar beet is an economically important crop and one of the major sources of sucrose around the world. Beet necrotic yellow vein virus (BNYVV) and Beet severe curly top virus (BSCTV) are two widespread viruses in sugar beet that cause severe damage to its performance. Previously, we have successfully produced resistance to BNYVV based on RNA silencing in sugar beet by introducing constructs carrying the viral coat-protein-encoding DNA sequence, CP21, in sense and anti-sense orientations. Yet, the RNA silencing-mediated resistance to a specific virus could be affected by other ones as a part of synergistic interactions. In this study, we assayed the specificity of the induced resistance against BNYVV in two sets of transgenic events, S3 and S6 carrying 5'-UTR with or without CP21-coding sequences, respectively. These events were subjected to viral challenges with either BNYVV, an Iranian isolate of BSCTV (BSCTV-Ir) or both. All the plants inoculated with just BSCTV-Ir displayed curly-leaf symptoms. However, partial resistance was evident in S3 events as shown by mild symptoms and reduced PCR amplification of the BSCTV-Ir coat protein encoding sequence. Based on the presented data, resistance to BNYVV was stable in almost all the transgenic plants co-infected with BSCTV-Ir, except for one event, S3-229. In general, it seems that the co-infection does not affect the resistance to BNYVV in transgenic plants. These findings demonstrated that the introduced RNA silencing-mediated resistance against BNYVV in transgenic sugar beets is specific and is not suppressed after co-infection with a heterologous virus.

Prevalence and co-infections of pathogenic bacteria in Nile tilapia broodstock farms: implications for aquaculture management in Togo.

This study aimed to evaluate the prevalence of E. coli, Pseudomonas spp., and Enterococcus spp. in Nile tilapia broodstock farms in Togo and their association with fish diseases. In total, 60 samples were collected from two tilapia broodstock farms, including 40 broodstock tilapia and 20 water samples. Each farm had concrete tanks supplied with water from two drills. Of the 40 fish samples, 20 were healthy, and the other 20 were diseased. Microbiological analysis of samples was conducted using standardized methods. The study revealed significant contamination in all collected water samples, detecting multiple bacterial populations. Bacterial infections were more prevalent in symptomatic fish, with 85% exhibiting co-infections (df = 1, χ2 = 7.03, p = 0.008). Contamination levels varied among sample types, with higher counts observed in wastewater (E. coli: 0-300 CFU/mL, Pseudomonas spp.: 3-300 CFU/mL, Enterococcus spp.: 0-55 × 102 CFU/mL) compared to drilling water (Pseudomonas spp.: 0-300 CFU/mL, E. coli: 3-400 CFU/mL, Enterococcus spp.: 0-14 × 102 CFU/mL), and intestinal samples (E. coli: 0-120 × 102 CFU/mL, Enterococcus spp.: 0-170 × 102 CFU/mL, Pseudomonas spp.: 0-60 × 102 CFU/mL) (df = 21, χ2 = 59.31, p < 0.000). Our findings emphasize the significant prevalence of pathogenic bacteria in Nile tilapia broodstock farms in Togo, highlighting the importance of water quality management and infection control strategies. Further studies are required to develop appropriate prevention strategies.

Multispecies coinfections and presence of antibiotics shape resistance and fitness costs in a pathogenic bacterium.

Increasing antimicrobial resistance (AMR) poses a challenge for treatment of bacterial diseases. In real life, bacterial infections are typically embedded within complex multispecies communities and influenced by the environment, which can shape costs and benefits of AMR. However, knowledge of such interactions and their implications for AMR in vivo is limited. To address this knowledge gap, we investigated fitness-related traits of a pathogenic bacterium (Flavobacterium columnare) in its fish host, capturing the effects of bacterial antibiotic resistance, coinfections between bacterial strains and metazoan parasites (fluke Diplostomum pseudospathaceum) and antibiotic exposure. We quantified real-time replication and virulence of sensitive and resistant bacteria and demonstrate that both bacteria can benefit from coinfection in terms of persistence and replication, depending on the coinfecting partner and antibiotic presence. We also show that antibiotics can benefit resistant bacteria by increasing bacterial replication under coinfection with flukes. These results emphasize the importance of diverse, inter-kingdom coinfection interactions and antibiotic exposure in shaping costs and benefits of AMR, supporting their role as significant contributors to spread and long-term persistence of resistance.

Low-cost molecular methods to characterise gastrointestinal nematode co-infections of goats in Africa.

BACKGROUND: Veterinary diagnostics aid intervention strategies, track zoonoses, and direct selective breeding programs in livestock. In ruminants, gastrointestinal nematode (GIN) parasites are a major cause of production losses, but morphologically similar species limit our understanding of how specific GIN co-infections impact health in resource-limited settings. To estimate the presence and relative abundance of GINs and other helminths at the species level, we sought to develop a low-cost and low-resource molecular toolkit applied to goats from rural Malawi smallholdings. METHODS: Goats were subjected to health scoring and faecal sampling on smallholdings in Lilongwe district, Malawi. Infection intensities were estimated by faecal nematode egg counts with a faecal subsample desiccated for DNA analysis. Two DNA extraction methods were tested (low-resource magbead kit vs high-resource spin-column kit), with resulting DNA screened by endpoint polymerase chain reaction (PCR), semi-quantitative PCR, quantitative PCR (qPCR), high-resolution melt curve analysis (HRMC), and 'nemabiome' internal transcribed spacer 2 (ITS-2) amplicon sequencing. RESULTS: Both DNA isolation methods yielded comparable results despite poorer DNA purity and faecal contaminant carryover from the low-resource magbead method. GINs were detected in 100% of samples regardless of infection intensity. Co-infections with GINs and coccidia (Eimeria spp.) were present in most goats, with GIN populations dominated by Haemonchus contortus, Trichostrongylus colubriformis, Trichostrongylus axei, and Oesophagostomum columbianum. Both multiplex PCR and qPCR were highly predictive of GIN species proportions obtained using nemabiome amplicon sequencing; however, HRMC was less reliable than PCR in predicting the presence of particular species. CONCLUSIONS: These data represent the first 'nemabiome' sequencing of GINs from naturally infected smallholder goats in Africa and show the variable nature of GIN co-infections between individual animals. A similar level of granularity was detected by semi-quantitative PCR methods, which provided an accurate summary of species composition. Assessing GIN co-infections is therefore possible using cost-efficient low-resource DNA extraction and PCR approaches that can increase the capacity of molecular resources in areas where sequencing platforms are not available; and also open the door to affordable molecular GIN diagnostics. Given the diverse nature of infections in livestock and wildlife, these approaches have potential for disease surveillance in other areas.

COVID-19 testing protocols to guide duration of isolation: a cost-effectiveness analysis.

BACKGROUND: The Omicron variant of SARS-CoV-2 led to a steep rise in transmissions, and emerging variants continue to influence case rates across the US. As public tolerance for isolation abated, CDC guidance on duration of at-home isolation of COVID-19 cases was shortened to five days if no symptoms, with no laboratory test requirement, despite more cautious approaches advocated by other federal experts. METHODS: We conducted a decision tree analysis of alternative protocols for ending COVID-19 isolation, estimating net costs (direct and productivity), secondary infections, and incremental cost-effectiveness ratios. Sensitivity analyses assessed the impact of input uncertainty. RESULTS: Per 100 individuals, five-day isolation had 23 predicted secondary infections and a net cost of $33,000. Symptom check on day five (CDC guidance) yielded a 23% decrease in secondary infections (to 17.8), with a net cost of $45,000. Antigen testing on day six yielded 2.9 secondary infections and $63,000 in net costs. This protocol, compared to the next best protocol of antigen testing on day five of a maximum eight-day isolation, cost an additional $1,300 per secondary infection averted. Antigen or polymerase chain reaction testing on day five were dominated (more expensive and less effective) versus antigen testing on day six. Results were qualitatively robust to uncertainty in key inputs. CONCLUSIONS: A six-day isolation with antigen testing to confirm the absence of contagious virus appears the most effective and cost-effective de-isolation protocol to shorten at-home isolation of individuals with COVID-19.

Assessment and management of secondary bacterial infections complicating Mpox (Monkeypox) using a telemedicine service. A prospective cohort study.

INTRODUCTION: During spring 2022, an outbreak of Monkeypox (mpox) emerged as an infection of concern in Europe. Due to the overlapping clinical features of mpox and bacterial infections, diagnosis of concomitant bacterial infection is challenging. In this prospective cohort study, we report the incidence, severity, and progression of patients with secondary bacterial infection complicating mpox infection. METHOD: Data were collected via a bespoke mpox telemedicine service provided by Infection services at North Manchester General Hospital, UK. A diagnosis of secondary bacterial infection was based on the history (balanitis, surrounding erythema, purulent discharge and nasal ulceration) and review of patient-collected medical photography. Patient were reviewed face-to-face where necessary. RESULTS: Secondary bacterial infection was diagnosed in 15 of 129 (11.6%) patients with mpox. Three patients with secondary bacterial infection (3/129, 2.3%) required admission to hospital and one patient underwent surgical debridement. Median healing (thus, isolation) times were longer in those with bacterial infection. DISCUSSION: In this prospective cohort study of patients with mpox, secondary bacterial infection was infrequent and predominantly mild. The virtual ward and telemedicine follow up allowed for the prompt recognition of secondary bacterial infections and timely antibiotic administration. Due to concerns regarding nosocomial transmission, mild clinical course and limited inpatient bed capacity, we believe this model of outpatient management for mpox (Clade II B.1 lineage) could be replicated in other low risk populations where suitable home isolation facilities exist.

Assessment of Pediatric Telemedicine Using Remote Physical Examinations With a Mobile Medical Device: A Nonrandomized Controlled Trial.

Importance: The number of innovations in health care based on the use of platforms, digital devices, apps, and artificial intelligence has grown exponentially in recent years. When used correctly, these technologies allow inequities in access to health care to be addressed by optimizing care and reducing social and geographic barriers. However, most of the technological health care solutions proposed have not undergone rigorous clinical studies. Objective: To assess the concordance between measurements from a remote physical examination using a mobile medical device and measurements from a conventional in-person physical examination. Design, Setting, and Participants: This nonrandomized controlled trial was conducted from January 1 to December 31, 2020. The clinical parameters compared were heart rate; body temperature; heart, lung, and abdominal auscultation; otoscopy; throat and oral examination; and skin examination. A total of 690 patients with clinical stability and various symptoms who were seen in the emergency department of 2 Brazilian pediatric hospitals were eligible to enter this study. Main Outcomes and Measures: The primary outcome was concordance between measurements from a telemedicine physical examination using a mobile medical device and measurements from a conventional in-person physical examination. The secondary outcome was the specificity and sensitivity of the digital device, considering the conventional in-person consultation as the gold standard. Results: Among 690 patients, the median (IQR) age at study entry was 5 (1-9) years; 348 (50.4%) were female, and 331 (48.0%) presented with a chronic disease. Regarding the primary outcome, the concordance values were 90% or greater for skin examination (94% for rash, 100% for hemorrhagic suffusion, and 95% for signs of secondary infection), characteristics of the mucosa (98% for hydration and 97% for coloring), and heart (95% for murmur, 97% for rhythms, and 98% for sounds), lung (91% for adventitious sounds, 97% for vesicular sounds, and 90% for fever), and abdominal (92% for abdominal sounds) auscultations. Concordance values were lower for otoscopy (72% for the ear canal and 86% for the tympanic membrane), throat and oral examination (72%), and rhinoscopy (79% for mucosa and 81% for secretion). The specificity was greater than 70% (ranging from 74.5% for the ear canal to 99.7% for hemorrhagic suffusion) for all variables. The sensitivity was greater than 52% for skin examination (58.0% for rash and 54.8% for signs of secondary infection), throat and oral examination (52.7%), and otoscopy (66.1% for the ear canal and 64.4% for the tympanic membrane). Conclusions and Relevance: In this study, measurements from remote physical examination with a mobile medical device had satisfactory concordance with measurements from in-person physical examination for otoscopy, throat and oral examination, skin examination, and heart and lung auscultation, with limitations regarding heart and lung auscultation in infants and abdominal auscultation in children of all ages. Measurements from remote physical examination via a mobile medical device were comparable with those from in-person physical examination in children older than 2 years. These findings suggest that telemedicine may be an alternative to in-person examination in certain contexts and may help to optimize access to health care services and reduce social and geographic barriers. Trial Registration: Brazilian Registry of Clinical Trials Identifier: RBR-346ymn.

Risk factors analysis and risk assessment model construction of systemic lupus erythematosus patients with infection.

OBJECTIVE: To analyze the characteristics of peripheral blood lymphocyte subsets in systemic lupus erythematosus (SLE) patients with infection and non-infection group. Explore the risk factors of infection in SLE patients and establish a risk matrix model to predict the occurrence of co-infection. METHODS: total of 333 SLE patients without infection, 163 patients suffering from infection, and 132 healthy controls (HCs) were recruited. General clinical data and disease activity indicators were collected. The levels of total T, B, CD4+T, CD8+T, NK, Th1, Th2, Th17, and Treg cells in peripheral blood of HCs, SLE patients (including infected and non-infected group) were analyzed by flow cytometry. The risk assessment model was constructed, and the receiver operating characteristic curve was drawn. 39 SLE patients with infection and 20 patients without infection were randomly selected to evaluate the predictive power of the regression model. RESULTS: The levels of T, B, CD4+T, CD8+T, and NK cells in the infected patients were significantly decreased when compared with that of both non-infected patients and HCs (p < .05). The non-infected patients had a higher level of Th17 than that of HCs (p < . 05), but the absolute numbers of Th17 in infected patients was the lowest among the three groups (p < .001). The number of Treg cells in SLE patients was significantly lower than that of HCs (p < .01), and the infected patients had the fewest Treg cells among all these groups (p < . 05). A risk assessment model for SLE with infection was established, p = 1/(1-e-y), Y = 1.763-0.004 × Absolute number of CD4 + T cells-0.005 × Absolute number of NK cells -0.005 × Platelet count(×1012/L) + 1.033 × Absolute number of lymphocytes (×109/L) + 0.023 × C-reactive protein (mg/dL), whose predictive sensitivity is 77.5%, and specificity is 78.3%. CONCLUSION: The new risk assessment model exhibits good predictive ability to assess co-infection risk in SLE patients. T cells, NK cells, and CD4 + T cells along with other parameters help in differentiating Lupus with infection from Lupus alone.

Assessment of Risk Factors and Clinical Outcomes in Hospitalized COVID-19 Patients with Candida spp. Co-infections: Species Distribution and Antifungal Susceptibility Patterns of Isolates.

INTRODUCTION: Fungal co-infections are considered an important complication in hospitalized patients with SARS-CoV-2 that can be attributed to disease aggravation, increased mortality, and poor outcomes. This study was conducted to determine the species distribution and antifungal susceptibility patterns of Candida isolates from hospitalized COVID-19 patients in Shiraz, Iran, in addition to associated risk factors and outcomes of co-infections with Candida species. MATERIALS AND METHODS: In this single-center study, a total of 106 hospitalized COVID-19 patients were evaluated for clinical characteristics and outcomes. Species identification was performed by ITS1-5.8S-ITS2 gene sequencing. Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, amphotericin B, and nystatin was determined according to the M27-A3/S4 CLSI protocol. RESULTS: Candida species were recovered from 48% (51/106) of hospitalized COVID-19 patients. Statistical analysis showed that patients who had heart failure, bacterial co-infection, and were receiving empirical antifungal therapy had a higher risk of developing Candida co-infection. In total, 71 Candida isolates were recovered, of which C. albicans (69%) was the most prevalent isolate. The majority of the Candida isolates were susceptible to all classes of tested antifungal drugs. DISCUSSION: Our results elucidate a high rate of Candida co-infections among hospitalized COVID-19 patients. Comorbidities such as heart failure, HTN, COPD, bacterial infections as well as therapeutic interventions including catheterization, mechanical ventilation, and ICU admission increased the risk of Candida spp. isolation from the bloodstream, respiratory tract and urine samples, which led to a higher in-hospital mortality rate. Additionally, obtained data clarified that empirical antifungal therapy was not as successful as anticipated.

SARS-CoV-2 and dengue virus co-infection: Epidemiology, pathogenesis, diagnosis, treatment, and management.

SARS-CoV-2 and dengue virus co-infection cases have been on the rise in dengue-endemic regions as coronavirus disease 2019 (COVID-19) spreads over the world, posing a threat of a co-epidemic. The risk of comorbidity in co-infection cases is greater than that of a single viral infection, which is a cause of concern. Although the pathophysiologies of the two infections are different, the viruses have comparable effects within the body, resulting in identical clinical symptoms in the case of co-infection, which adds to the complexity. Overlapping symptoms and laboratory features make proper differentiation of the infections important. However, specific biomarkers provide precise results that can be utilised to diagnose and treat a co-infection, whether it is simply COVID-19, dengue, or a co-infection. Though their treatment is distinguished, it becomes more complicated in circumstances of co-infection. As a result, regardless of whatever infection the first symptom points to, confirmation diagnosis of both COVID-19 and dengue should be mandatory, particularly in dengue-endemic regions, to prevent health deterioration in individuals treated for a single infection. There is still a scarcity of concise literature on the epidemiology, pathophysiology, diagnosis, therapy, and management of SARS-CoV-2 and dengue virus co-infection. The epidemiology of SARS-CoV-2 and dengue virus co-infection, the mechanism of pathogenesis, and the potential impact on patients are summarised in this review. The possible diagnosis with biomarkers, treatment, and management of the SARS-CoV-2 and dengue viruses are also discussed. This review will shed light on the appropriate diagnosis, treatment, and management of the patients suffering from SARS-CoV-2 and dengue virus co-infection.