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Mucormycosis represents several unusual opportunistic infection caused by saprophytic aseptate fungi. There is a recent rise in cases of mucormycosis due to an increase in diabetic and immunodeficient patients like patients on long-term steroids, immunomodulators due to organ transplantation, malignancies, mainly haematological malignancies, and autoimmunity. Anatomically, mucormycosis can be localised most commonly as rhino-orbito-cerebral followed by pulmonary, disseminated, cutaneous and gastrointestinal, rarest being small intestinal. Patients with Down syndrome are immunodeficient due to their impaired immune response. Disseminated tuberculosis is also common in immunodeficient patients. We report a rare case of small intestinal mucormycosis in a patient with Down syndrome with coexisting intestinal tuberculosis. Due to the invasiveness of mucormycosis, the patient succumbed to death despite providing aggressive surgical debridement and medical management.

Hepatitis C virus (HCV) infection is common among people living with HIV. HIV and HCV coinfected patients have higher overall mortality rates compared with HIV mono-infected patients. With its high cure rate of HCV infection, direct-acting antiviral (DAA) treatment provides an opportunity to improve the survival of the HIV/HCV coinfected population. The objective of this study is to investigate the association between DAA treatment and all-cause mortality among HIV/HCV coinfected people. The study included 7103 Medicare beneficiaries in the United States who were infected with both HIV and HCV between 2014 and 2017. Cox proportional hazards regression model was used to estimate adjusted hazard ratios (aHRs) of death for patients with and without DAA treatment while controlling for patient characteristics. During the study period, 1675 patients initiated DAA treatment (23.6%). The adjusted hazard ratio (aHR) of all-cause mortality between patients with and without DAA treatment was 0.37 (95% CI, 0.29-0.48), regardless of cirrhosis status. DAA treatment was associated with a smaller reduction in all-cause mortality for females (aHR, 0.50 [95% CI, 0.30-0.85]) compared with males (aHR, 0.34 [95% CI, 0.25-0.46]). DAA treatment was associated with improved survival among all HIV/HCV coinfected patients regardless of sex or HCV disease progression.

INTRODUCTION: We assessed the possible relationship between the COVID-19 with laboratory-confirmed CL-registered cases with a history of scar compared with healthy volunteer participants. METHODS: This case-control retrospective study was conducted in southeastern Iran with a high anthroponotic cutaneous leishmaniasis (ACL) burden. RESULTS: Overall, n=1,010 cases of CL consisting of n=479 male and n=531 female were analyzed for probable infection with SARS-CoV-2. Altogether, in the case group, two men and one woman (0.3%) were afflicted with a mild form of COVID-19 disease, and none of them were hospitalized or died. In contrast, out of n=2,020 healthy participants, n=57 (2.9%) contracted laboratory-confirmed COVID-19, including mild (66.7%), hospitalized (26.3%) and critical and death (3.5%, each). There was a strong negative association between CL infection and COVID-19. The burden of COVID-19 in CL-cured participants significantly reduced the morbidity (OR=0.12, CI: 0.03 - 0.30 and P

Background and Aims Chronic hepatitis B (CHB) infection remains the most frequent etiology of hepatocellular carcinoma globally as well as a major cause of cirrhosis. Despite vaccination, substantial numbers of persons have already been infected with hepatitis B virus and remain at risk of progressive liver disease. Methods In 2004, a CHB management algorithm was developed by a panel of North American hepatologists which was subsequently updated in 2006, 2008, and 2015. Since the most recent version, several developments have altered the management of CHB. Tenofovir alafenamide, with a more favorable safety profile than tenofovir disoproxil fumarate, has been introduced as an initial antiviral choice as well as an alternative for long-term therapy. Quantitation of hepatitis B surface antigen (HBsAg) is becoming more widely available in clinical practice, with implications for monitoring response to treatment. Additionally, there has been a shift in how the natural history of CHB is perceived as newer evidence has challenged the concept that during the immunotolerant phase of infection disease progression is not a concern. Finally, recent analyses indicate that in the United States, the average age of CHB patients has increased implying that the presence of comorbidities including metabolic liver disease increasing use of biologics associated with aging will increasingly affect disease management. Results This updated algorithm is intended to serve as a guide to manage CHB while new antiviral strategies are developed. Conclusions Recommendations have been based on evidence from the scientific literature, when possible, as well as clinical experience and consensus expert opinion. Points of continued debate and areas of research need are also described.

BackgroundThe prevalence, association with disease status, and public health impact of infection with mixtures of M. tuberculosis strains is unclear, in part due to limitations of existing methods for detecting mixed infections.MethodsWe developed an algorithm to identify mixtures of M. tuberculosis strains using next generation sequencing data, assessing performance using simulated sequences. We identified mixed M. tuberculosis strains when there was at least one mixed nucleotide position, and where both the mixture’s components were present in similar isolates from other individuals. We determined risk factors for mixed infection among isolations of M. tuberculosis in England using logistic regression. We used survival analyses to assess the association between mixed infection and putative transmission.Findings6,560 isolations of TB were successfully sequenced in England 2016-2018. Of 3,691 (56%) specimens for which similar sequences had been isolated from at least two other individuals, 341 (9.2%) were mixed. Infection with lineages other than Lineage 4 were associated with mixed infection. Among the 1,823 individuals with pulmonary infection with Lineage 4 M. tuberculosis, mixed infection was associated with significantly increased risk of subsequent isolation of closely related organisms from a different individual (HR 1.43, 95% CI 1.05,1.94), indicative of transmission.InterpretationMixtures of transmissible strains occur in at least 5% of tuberculosis infections in England; when present in pulmonary disease, such mixtures are associated with an increased risk of tuberculosis transmission.FundingPublic Health England; NIHR Health Protection Research Unit Oxford; European Union.Research in ContextEvidence Before This StudyWe searched Pubmed using the search terms ‘tuberculosis’ and ‘mixed’ or ‘mixture’ for English Language articles published up to 1 April 2019. Studies, most performed without the benefit of genomic sequencing, report mixed TB infection from a range of medium and high prevalence areas and show it to be associated with delayed treatment response. Modelling suggests detection and treatment of mixed TB infection is an important goal for TB eradication campaigns. Although routine DNA sequencing of M. tuberculosis isolates is becoming widespread, efficient methods for detecting mixed infection from such data are underdeveloped, and the true prevalence of mixed infection and its association with transmission is unclear.Added Value of This StudyThis study investigated a large series of TB isolations obtained as part of a routine Mycobacterial sequencing program by two reference laboratories, in a low incidence area, England. We developed an efficient generalisable approach to identify transmitted mixed M. tuberculosis infection; our approach is capable of sensitive and specific detection of a single mixed nucleotide position. We identified mixed infection of similar strains (‘microvariation’) in about 9.2% of the M. tuberculosis samples which we were able to assess, and found evidence of increased transmission from individuals with mixed infection.Implications of All the Available EvidenceTB microvariation is a risk factor for TB transmission, even in the low incidence area studied. Although an efficient and highly specific technique identifying microvariation exists, it relies on comparison with similar sequences isolated from other patients. Sharing of sequence data from the many TB sequencing programs being deployed globally will increase the sensitivity of microvariation detection, and may assist targeted public health interventions.

The impact of HIV antiretroviral therapy (ART) on immune dysregulation associated with hepatitis C virus (HCV)/HIV coinfection is incompletely understood. We serially assessed monocyte activation (neopterin, sCD14, and sCD163) and T cell activation (HLA-DR, CD38) and immune exhaustion [program cell death protein 1 (PD1), TIGIT] in HIV/HCV-coinfected individuals who participated in a randomized trial performed in Vietnam designed to assess the hepatotoxicity of raltegravir (RAL)- versus efavirenz (EFV)-based therapy when used as first-time ART in combination with tenofovir disoproxil fumarate and emtricitabine. Baseline pre-ART values were compared with those from ART-naive HIV-monoinfected and HIV-seronegative individuals. Before ART, HIV/HCV-coinfected individuals had higher levels of neopterin, sCD14, and sCD163, and increased frequencies of CD38(+)HLA-DR(+), PD1(+), and TIGIT(+) CD4 and CD8 T cells compared with ART-naive HIV-monoinfected or HIV-seronegative individuals (all p

Background Secondary pulmonary infections (SPI) have not been well described in COVID-19 patients. Our study aims to examine the incidence and risk factors of SPI in hospitalized COVID-19 patients with pneumonia. Methods This was a retrospective, single-center study of adult COVID-19 patients with radiographic evidence of pneumonia admitted to a regional tertiary care hospital. SPI was defined as microorganisms identified on the respiratory tract with or without concurrent positive blood culture results for the same microorganism obtained at least 48 hours after admission. Results Thirteen out of 244 (5%) had developed SPI during hospitalization. The median of the nadir lymphocyte count during hospitalization was significantly lower in patients with SPI as compared to those without SPI [0.4 K/uL (IQR 0.3-0.5) versus 0.6 K/uL (IQR 0.3-0.9)]. Patients with lower nadir lymphocyte had an increased risk of developing SPI with odds ratio (OR) of 1.21 (95% CI: 1.00 to 1.47, p=0.04) per 0.1 K/uL decrement in nadir lymphocyte. The baseline median inflammatory markers of CRP [166.4 mg/L vs. 100.0 mg/L, p=0.01] and D-dimer (18.5 mg/L vs. 1.4 mg/L, p

Background/purpose Influenza is frequently complicated with bacterial co-infection. This study aimed to disclose the significance of Streptococcus pneumoniae co-infection in children with influenza. Methods We retrospectively reviewed medical records of pediatric patients hospitalized for influenza with or without pneumococcal co-infection at the National Taiwan University Hospital from 2007 to 2019. Clinical characteristics and outcomes were compared between patients with and without S. pneumoniae co-infection. Results There were 558 children hospitalized for influenza: 494 had influenza alone whereas 64 had S. pneumoniae co-infection. Patients with S. pneumoniae co-infection had older ages, lower SpO2, higher C-Reactive Protein (CRP), lower serum sodium, lower platelet counts, more chest radiograph findings of patch and consolidation on admission, longer hospitalization, more intensive care, longer intensive care unit (ICU) stay, more mechanical ventilation, more inotropes/vasopressors use, more surgical interventions including video-assisted thoracoscopic surgery (VATS) and extracorporeal membrane oxygenation (ECMO), and higher case-fatality rate. Conclusion Compared to influenza alone, patients with S. pneumoniae co-infection had more morbidities and mortalities. Pneumococcal co-infection is considered when influenza patients have lower SpO2, lower platelet counts, higher CRP, lower serum sodium, and more radiographic patches and consolidations on admission.

BACKGROUND/PURPOSE Direct-acting antiviral agents (DAAs) have revolutionized the paradigm for HCV treatment. However, patients with HBV and HCV co-infection receiving DAAs are at significant risk of HBV reactivation, with limited literature addressing the roles of serum chemokines/chemokines. We aimed to explore the profiles and predictive value of serum cytokines/chemokines regarding HBV reactivation in this clinical setting. METHODS From 2017 to 2019, 25 patients with HBV and HCV co-infection scheduled for DAA therapy were prospectively enrolled. At enrolment and after DAA treatment, serial serum cytokine/chemokine levels were examined. The baseline and dynamic levels were compared between those with versus without HBV virologic (defined by an increase of serum HBV DNA to >10 times) and clinical reactivation (defined by > 1.5-fold elevated ALT level than nadir and >100 U/L; or > 2-fold increase from nadir and greater than the upper normal limit, in addition to virologic reactivation). RESULTS There were 20 patients (80%) experiencing HBV virologic reactivation and 6 patients (24%) experiencing clinical reactivation. Patients with clinical reactivation had higher pre-treatment TNF-alpha (27.93 versus 18.85 pg/mL, P = 0.015), lower week-4 IFN-gamma (1.07 versus 8.74 pg/mL, P = 0.020) levels and significant declines of CCL2 and TNF-alpha (P

This study aimed to determine whether there is a difference in the risk of death/critical illness between different stages of hepatitis B virus (HBV) (resolved hepatitis B, HBeAg (-) chronic hepatitis B [CHB]/infection, HBeAg (+) CHB/infection, and HBV reactivation) coinfected with coronavirus disease 2019 (COVID-19); and if there is a difference, whether it is due to abnormal liver function and to what extent.This cohort study included all COVID-19 inpatients of a single-center tertiary care academic hospital in Wuhan, Hubei, China, between February 4, 2020, and follow-up to April 14, 2020. A total of 2899 patients with COVID-19 were included as participants in this study, and they were divided into five groups based on hepatitis B infection status. Follow-up was conducted for mortality and ICU admission during hospitalization.The median follow-up time was 39 days (IQR, 30-50), with 66 deaths and 126 ICU admissions. After adjustment, compared with patients without CHB, the hazard ratio (HR) for ICU admission was 1.86 (95% CI: 1.05-3.31) for patients with HBeAg (+) CHB/infection. The HR for death was 3.19 (95% CI: 1.62-6.25) for patients with HBeAg (+) CHB/infection. The results for the mediating effect indicated that the total effect of HBeAg (+) CHB/infection on death/ICU stay was partially mediated by abnormal liver function, which accounted for 79.60% and 73.53%, respectively.Patients with COVID-19 coinfected with HBV at the HBeAg (+) CHB/infection stage have an increased risk of poor prognosis, and abnormal liver function partially mediates this increased risk of poor prognosis caused by the coinfection.

Introduction The 2015 dengue outbreak in southern Taiwan caused substantial mortality. We analyzed the causes of death among these patients. Materials and methods This retrospective study was conducted at a medical center in Tainan from August 2015 to December 2015. Dengue was diagnosed based on the detection of serum dengue NS1 antigen, IgM, or viral RNA in the blood. Causes of death were retrieved from chart reviews by three clinicians. Results There were 4488 cases of dengue in the study hospital, with an in-hospital fatality rate of 1.3% (60 cases). The mean age of the 60 fatal cases was 73 years, among whom 90% were aged ≥65 years. Twenty-eight (46.7%) patients died of severe dengue, and 29 (48.3%) deaths were possibly related to dengue. Of the latter, 24 (40%) died of secondary infections. Thirteen cardiac arrest events, including out-of-hospital (5 events) and in-hospital (8) cardiac arrests in the emergency department, occurred during the dengue epidemic. Seven (53.8%) patients did not receive medical aid before the event. Of the 40 deaths that occurred within one week after hospitalization, 60% died of severe dengue. In contrast, 50% of 20 deaths that occurred one week after hospitalization were related to hospital-acquired infections, mainly pneumonia. Conclusion Of 60 fatal cases, with a predominance of elderly patients, deaths were related to severe dengue within the first week after admission and secondary infections thereafter. The absence of medical care before cardiac arrest events highlights the importance of health education for warning signs of dengue.

Introduction Coinfections of influenza and other respiratory viruses (ORVs) are frequent in the epidemic season. The aim of this study was to examine the demographic and virological variables associated with coinfections by influenza and ORVs. Materials and methods We analysed respiratory samples of patients with laboratory-confirmed influenza using molecular diagnostic methods obtained in 8 consecutive influenza seasons (2011–2012 to 2018–2019). We analysed data focusing on different variables: age, sex, type of patient (hospitalized/sentinel) and detected type/subtype of influenza. Results Coinfections of influenza and ORVs were detected in 17.8% of influenza-positive samples. The probability of detecting coinfection was significantly higher in young children (0–4 years; OR: 2.7; 95% CI: 2.2–3.4), children (5–14 years; OR: 1.6; 95% CI: 1.2–2.1) and patients infected with the A(H3N2) subtype (OR: 1.4; 95% CI: 1.14–1.79). Also, we found a significantly higher frequency of coinfections involving influenza and 2 or more other respiratory viruses in young children (0–4 years; OR: 0.5; 95% CI: 0.32–0.8), adults (40–64 years; OR: 0.5; 95% CI: 0.3–0.9) and women (OR: 0.7; 95% CI: 0.5–0.9). Discussion These results show that coinfections of influenza and ORVs are more frequent in young children and children, and in cases involving the A(H3N2) influenza subtype. Our findings can be useful to guide the use of multiplex diagnostic methods in laboratories with limited resources.

Corynebacterium macginleyi has long been associated with ocular infections and has more recently been rarely implicated in systemic infections. There is a paucity of literature regarding the rate of C. macginleyi co-infection with other bacterial and viral pathogens and regarding the incidence of C. macginleyi infection in the paediatric population. In this study, we report 30 isolates of C. macginleyi of ocular origin from 26 patients, identified using matrix-assisted laser desorption ionisation-time of flight mass spectrometry (MALDI-TOF MS). The rates of co-isolation with bacterial and viral pathogens were 62% (n=16/26) and 39% (n=5/13), respectively, in this study. Of these, 13 patients had molecular testing performed as requested by treating clinicians for either the Chlamydia trachomatis/Neisseria gonorrhoeae PCR or herpes/enterovirus/adenovirus multiplex PCR. All isolates tested susceptible to linezolid, vancomycin and ciprofloxacin, with variable resistance to tetracycline, clindamycin and penicillin using EUCAST breakpoints.

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40–60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.

Peripheral artery disease (PAD) is associated with decreased physical function and increased mortality in the general population. We previously found that PAD is common in middle-aged women with and without HIV infection, but its association with functional decline is unclear. We examine the contribution of PAD to functional decline in the Women's Interagency HIV Study, controlling for traditional cardiovascular risk factors and HIV-related factors.Analysis included 1839 participants (72% with HIV) with measured ankle-brachial index (ABI) and 4 m gait speed. ABI values categorized PAD severity. Linear models with repeated measures estimated the association of PAD severity with log-transformed gait speed after controlling for demographic, behavioral, and metabolic risk factors, and HIV/hepatitis C virus status.Median age was 50 years and more than 70% were Black. Compared with normal ABI, there was a dose-response relationship between increasing PAD severity and slower gait speed in univariable analyses: 6% slower gait speed for low-normal ABI [95% confidence interval (CI): 4-9%], 10% for borderline PAD (95% CI: 6-13%), 14% for mild PAD (95% CI: 9-18%), and 16% for moderate-severe PAD (95% CI: 5-25%). PAD severity remained associated with slower gait speed in multivariable analyses. HIV/hepatitis C virus co-infection was independently associated with 9% (95% CI: 4-14%) slower gait speed compared with those with neither infection. Among women with HIV, neither CD4+ cell count nor HIV-RNA level was associated with gait speed.In middle-aged women with and without HIV infection, greater PAD severity is associated with progressively slower gait speed. Early detection of subclinical PAD may decrease the risk of lower extremity functional impairment and its long-term health consequences.

Background:Evidence from pandemics suggests that influenza is often associated with bacterial coinfection. Among patients hospitalized for influenza pneumonia, we report the rate of coinfection and distribution of pathogens, and we compare outcomes of patients with and without bacterial coinfection.Methods:We included adults admitted with community-acquired pneumonia (CAP) and tested for influenza from 2010 to 2015 at 179 US hospitals participating in the Premier database. Pneumonia was identified using an International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) algorithm. We used multiple logistic and gamma-generalized linear mixed models to assess the relationships between coinfection and inpatient mortality, intensive care unit (ICU) admission, length of stay, and cost.Results:Among 38,665 patients hospitalized with CAP and tested for influenza, 4,313 (11.2%) were positive. In the first 3 hospital days, patients with influenza were less likely than those without to have a positive culture (10.3% vs 16.2%; P < .001), and cultures were more likely to contain Staphylococcus aureus (34.2% vs 28.2%; P = .007) and less likely to contain Streptococcus pneumoniae (24.9% vs 31.0%; P = .008). Of S. aureus isolates, 42.8% were methicillin resistant among influenza patients versus 53.2% among those without influenza (P = .01). After hospital day 3, pathogens for both groups were similar. Bacterial coinfection was associated with increased odds of in-hospital mortality (aOR, 3.00; 95% CI, 2.17–4.16), late ICU transfer (aOR, 2.83; 95% CI, 1.98–4.04), and higher cost (risk-adjusted mean multiplier, 1.77; 95% CI, 1.59–1.96).Conclusions:In a large US inpatient sample hospitalized with influenza and CAP, S. aureus was the most frequent cause of bacterial coinfection. Coinfection was associated with worse outcomes and higher costs.

Hepatitis C virus (HCV) infection is common in people living with HIV/AIDS (PLWHA). The advent of direct-acting antiviral agents (DAAs) has made HCV elimination a realistic goal. We conducted a retrospective cohort study using the US Medicare Fee-For-Service claims data and outpatient prescription drug data to assess the HCV DAA initiation and completion among newly diagnosed HIV-HCV-coinfected Medicare patients enrolled in 2014-2016. DAA initiation was defined as filling at least 1 prescription of DAAs during 2014-2016. DAA completion was defined as taking an 8-week or longer DAA treatment course for patients without cirrhosis and a 12-week or longer treatment duration for those with cirrhosis. Among 12 152 HIV-HCV-coinfected Medicare patients, 20.9% received the DAA treatment in 2014-2016. The average time from HCV diagnosis to DAA initiation was 277 days. The overall DAA completion rate was 92% among 2537 patients who used DAAs. Interventions are needed to improve DAA uptake in PLWHA.

Hepatitis viruses cause inflammation of the liver. Five major unrelated hepatitis viruses exist: hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis D virus (HDV), and hepatitis E virus (HEV). HAV and HEV are transmitted through the fecal-oral route and are most prevalent in areas of the world lacking proper sanitation of drinking water. These viruses cause acute infections that are cleared by the host immune system in the great majority of cases. On the other hand, HBV and HCV are the major causes of chronic hepatitis and liver disease that can progress to hepatocellular carcinoma. HBV is found in blood, semen, and other bodily fluids and is transmitted through sexual activity, injection-drug use, or perinatally. HCV is primarily transmitted through blood products. HDV is a defective virus that requires HBV infection for replication. Each hepatitis virus is in a distinct viral family and has unique molecular attributes.

Occult hepatitis B infection (OBI) is characterized by the detection of hepatitis B virus (HBV) DNA in serum or liver but negativity for hepatitis B surface antigen. OBI, which is thought to be maintained by host, immunological, viral and/or epigenetic factors, is one of the most challenging clinical features in the study of viral hepatitis. Currently, there is no validated detection test for OBI. It is believed that OBI is widely distributed throughout the world, with a higher prevalence in populations at high-risk HBV, but the detailed worldwide prevalence patterns are unknown. We conducted a survey of recently published studies on OBI rates across all continents. High prevalence rates of OBI are observed in some specific groups, including patients with hepatitis C virus, human immunodeficiency virus co-infection or hepatocellular carcinoma. In 2016, the World Health Organization adopted strategies to eliminate viral hepatitis by 2030, but the difficulties in detecting and treating OBI currently challenge this goal. Subjects with OBI can transmit HBV, and episodes of reactivation can occur. Further studies to understanding the mechanisms that drive the development of OBI are needed and can contribute to efforts at eliminating viral hepatitis.

This report describes a case of coinfection of Sphingomonas paucimobilis meningitis and Listeria monocytogenes bacteremia in a 66-year-old immunocompetent female patient. The patient had undergone traditional procedures, including acupuncture, which possibly caused the coinfection. During treatment with susceptible antibiotics for bacterial meningitis, she developed hydrocephalus on the third day. Consequently, the patient recovered with a mild neurological deficit of grade 4 motor assessment in both upper and lower extremities at discharge. S. paucimobilis and L. monocytogenes are rare pathogens in developed countries, occurring only during environmental outbreaks. S. paucimobilis meningitis is rarely reported. Hence, the various presentations of S. paucimobilis meningitis and the antibiotic regimen for its treatment are hereby reported, in addition to a review of other similar reported cases. This case is a possible traditional procedure-related infection. Appropriate oversight and training should be emphasized regarding preventive measures of this kind of infection. A team approach with neurologists and neurosurgeons is imperative in treating patients with hydrocephalus-complicated meningitis.

Purpose This study aimed to assess pathogen distributions and antimicrobial sensitivity characteristics in patients with non-small cell lung cancer (NSCLC) with severe radiation pneumonitis (SRP) and secondary infections. Methods and Materials Data from 1746 patients with NSCLC and SRP after thoracic radiation therapy from January 2009 to December 2020 were retrospectively analyzed. Pneumonia incidence, causative pathogens, and antibiotic resistance characteristics in patients with secondary lung infections were analyzed. Risk factors associated with mortality were identified through univariate and multivariate analyses. Antifungal drug efficacy and duration-related effects were assessed with Forest plots and receiver operating characteristic curves. Results Overall, 44.5% of patients with NSCLC and SRP (777 of 1746 patients) were diagnosed with secondary lung infections. In total, 899 bacterial strains were isolated from these patients, with Acinetobacter baumannii (n = 206; 27%), Klebsiella pneumonia (n = 200; 26.2%), and Pseudomonas aeruginosa (n = 104; 13.6%) being the most common. Carbapenems and cefoperazone-sulbactam resistance rates of 52.7% and 32.2%, 28.8% and 26.4%, and 23.7% and 20.2% were observed for these isolates, respectively. Infection-related deaths occurred in 22.4% of patients with SRP. Independent risk factors for infection-related death included poor performance status scores, inappropriate empirical antimicrobial treatment, bacteria/fungal coinfection, and lack of empirical antifungal treatment. Receiver operating characteristic curves showed that the cutoff value of empirical antifungal treatment duration was 9 (area under the curve: 0.819). Conclusions For patients with SRP and secondary lung infections, appropriate empirical antimicrobial treatment could decrease infection-related mortality, and cefoperazone-sulbactam may be an appropriate antibacterial drug. Empirical antifungal treatment for a minimum of 9 days might contribute to better outcomes. Although this represents a promising treatment approach for patients with SRP and secondary lung infections before antibacterial susceptibility testing, further prospective validation is essential.

Background Many patients with Coronavirus disease-2019 (Covid-19) present with radiological evidence of pneumonia. Because it is difficult to determine co-existence of bacterial pneumonia, many of these patients are initially treated with antibiotics. We compared the rates of bacterial infections and mortality in Covid-19 patients with pulmonary infiltrates versus patients diagnosed with ‘pneumonia’ the year previously. Methods We conducted a medical record review of patients admitted with Covid-19 and a pulmonary infiltrate and compared them with patients diagnosed with pneumonia admitted in the prior year before the pandemic. Data abstracted included baseline demographics, comorbidities, signs and symptoms, laboratory and microbiological results, and imaging findings. Outcomes were bacterial infections and mortality. Patients presenting with and without Covid-19 were compared using univariable and multivariable analyses. Results There were 1398 and 1001 patients admitted through the emergency department (ED) with and without Covid-19 respectively. Compared with non-Covid-19 patients, those with Covid-19 were younger (61±18 vs. 65±25 years, P

Background Biomarkers that can risk-stratify children with influenza virus lower respiratory infection may identify patients for targeted intervention. Early elevation of alveolar-related proteins in the bloodstream in these patients could indicate more severe lung damage portending worse outcomes. Methods We used a mouse model of human influenza infection and evaluated relationships between lung pathophysiology and surfactant protein D (SP-D), SP-A, and Club cell protein 16 (CC16). We then measured SP-A, SP-D and CC16 levels in plasma samples from 94 children with influenza-associated acute respiratory failure (PICFLU cohort), excluding children with underlying conditions explaining disease severity. We tested for associations between levels of circulating proteins and disease severity including the diagnosis of acute respiratory distress syndrome (ARDS), mechanical ventilator, intensive care unit and hospital days, and hospital mortality. Results Circulating SP-D showed a greater increase than SP-A and CC16 in mice with increased alveolar-vascular permeability following influenza infection. In the PICFLU cohort, SP-D was associated with moderate-severe ARDS diagnosis (p=0.01) and with mechanical ventilator (r =0.45, p=0.002), ICU (r=0.44, p=0.002), and hospital days (r = 0.37, p=0.001) in influenza infected children without bacterial coinfection. Levels of SP-D were lower in children with secondary bacterial pneumonia (p=0.01) and not associated with outcomes. CC16 and SP-A levels did not differ with bacterial coinfection and were not consistently associated with severe outcomes. Conclusions SP-D has potential as an early circulating biomarker reflecting degree of lung damage caused directly by influenza virus infection in children. Secondary bacterial pneumonia alters SP-D biomarker performance. This article is protected by copyright. All rights reserved.

Objectives The interaction of COVID-19 and tuberculosis (TB) are still poor characterized. Here we evaluated the immune response specific for Micobacterium tuberculosis (Mtb) and SARS-CoV-2 using a whole-blood-based assay-platform in COVID-19 patients either with TB or latent TB infection (LTBI). Methods We evaluated IFN-γ level in plasma from whole-blood stimulated with Mtb antigens in the Quantiferon-Plus format or with peptides derived from SARS-CoV-2 spike protein, Wuhan-Hu-1 isolate (CD4-S). Results We consecutively enrolled 63 COVID-19, 10 TB-COVID-19 and 11 LTBI-COVID-19 patients. IFN-γ response to Mtb-antigens was significantly associated to TB status and therefore it was higher in TB-COVID-19 and LTBI-COVID-19 patients compared to COVID-19 patients (p ≤ 0.0007). Positive responses against CD4-S were found in 35/63 COVID-19 patients, 7/11 LTBI-COVID-19 and only 2/10 TB-COVID-19 patients. Interestingly, the responders in the TB-COVID-19 group were less compared to COVID-19 and LTBI-COVID-19 groups (p = 0.037 and 0.044, respectively). Moreover, TB-COVID-19 patients showed the lowest quantitative IFN-γ response to CD4-S compared to COVID-19-patients (p = 0.0336) and LTBI-COVID-19 patients (p = 0.0178). Conclusions Our data demonstrate that COVID-19 patients either TB or LTBI have a low ability to build an immune response to SARS-CoV-2 while retaining the ability to respond to Mtb-specific antigens.

BACKGROUND: Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) coinfection through unheated blood product for hemophilia caused in early 1980s has been significantly serious problem in Japan. After the development of HIV treatment in 1990s, HCV-related hepatocellular carcinoma (HCC) has been one of the most significant problem in these population. Treatment choices for HCC might be limited in hemophilia patients because of their bleeding tendency. The aim of this study was to elucidate the treatment choices and outcome of HCC in hemophilic patients coinfected with HIV/HCV due to contaminated blood products. METHODS: We asked 444 Japanese centers that specialize in treating HIV patients for participation, whether they have HIV/HCV coinfected cases with HCC, and the patient characteristics, treatments for HCC and survival after treatments were retrospectively reviewed according to each institutional medical records. RESULTS: Of 444 centers, 139 centers (31%) responded to the first query, and 8 centers (1.8%) ultimately provided 26 cases of HCC in coinfected hemophilic patients, diagnosed between December 1999 and December 2017. All 26 were male hemophilic patients, with a median age at HCC diagnosis of 49 (range, 34–73) years. Thirteen cases (50%) were HCV-RNA positive, and 14 cases (54%) had a solitary tumor. Even in the cases of Child-Pugh grade A, only 1 case underwent resection, and 18 cases (69%) did not receive the standard treatment recommended by the Japanese Society of Hepatology. CONCLUSIONS: Hemophilic HCC patients with HIV/HCV coinfection may not routinely receive standard treatment due to their bleeding tendency and several complications related to HIV/HCV coinfection.

BACKGROUND & AIMS: Data on liver fibrosis evolution and its involvement in liver-related morbidity are scarce in individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infection during treatment. We identified profiles of liver fibrosis evolution in coinfected patients undergoing tenofovir (TDF). METHODS: We included 169 HIV-HBV-coinfected patients on TDF-based antiretroviral therapy. Virological and clinical data were obtained at TDF-initiation and every 6-12 months. From data on non-invasive liver fibrosis assessments collected yearly (FibroTest®), we established clusters of individuals with similar liver fibrosis evolution using group-based trajectory models. RESULTS: Four profiles of liver fibrosis evolution were established from a median follow-up of 7.6 years (IQR = 3.1-13.1): low fibrosis with no progression (29.6%, profile A), low fibrosis with progression (22.5%, profile B), moderate fibrosis with high fluctuation (39.6%, profile C), and cirrhosis with no regression (8.3%, profile D). When compared to profile A, baseline HBeAg-positive status was associated with profiles B (P = .007) and C (P = .004), older age with profiles C (P

We report a case of a pulmonary necrotizing sarcoid granulomatosis (NSG)-like lesion possibly associated with coinfection of Mycobacterium avium and Propionibacterium acnes. A solitary nodule in the right middle lobe of the lung was notable for coagulative necrosis with aggregates of sarcoid-like epithelioid granulomas. Small arteries were damaged by granulomas. Both M. avium and P. acnes were detected in the lesion. Furthermore, more P. acnes genomes were detected in the granulomas than in the non-lesion lung. These findings blur the pathophysiologic boundaries among NSG, sarcoidosis, and mycobacteriosis, and suggest that NSG needs to be recognized as continuous spectra of sarcoidosis/mycobcteriosis.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has changed the focus of healthcare and become a public health challenge around the world. The coinfection of SARS-CoV-2 with other microorganisms, including fungi, can cause difficult diagnosis and a worse prognosis. Pneumocystis jirovecii pneumonia (PJP) is a common opportunistic infection in human immunodeficiency virus (HIV) patients. However, sometimes the diagnosis is late presented after PJP finding on chest X-ray. We report a 24-year-old man with COVID-19 and PJP. Reverse transcriptase-polymerase chain reaction showed positive for SARS-CoV-2. HIV diagnosis was late presented after PJP finding on chest X-ray examination. HIV serology was positive with an absolute CD4+ count was 16 cells/mm3. He was treated with remdesivir IV, methylprednisolone IV, heparin, and cefoperazone-sulbactam IV. He was discharged after being admitted for 25 days. HIV treatment was started in outpatient services. Radiological diagnostic to diagnose concurrent COVID-19 and PJP pneumonia are important, especially in the setting where microscopic examination of sputum or Bronchoalveolar Lavage Fluid (BALF) is not available, or because BAL and sputum induction are aerosol-generating procedures that potentially increase the risk of COVID-19 transmission. HIV testing in COVID-19 patients was also should be considered as part of directed screening in patients presenting with features of PJP, especially for those with unknown HIV status. The determination of an appropriate corticosteroid dose is important to treat both COVID-19 and PJP with severe clinical features. Proper diagnosis and treatment co-infections are urgently needed in this current pandemic to reduce morbidity and mortality.

There are reports of high rates of antibiotic prescribing among hospitalized patients with COVID-19 around the world. To date, however, there are few reports of prescribing in relation to COVID-19 in Pakistan. Herein, we describe a point prevalence survey of antibiotic prescribing amongst patients hospitalized with suspected or proven COVID-19 in Pakistan. A Point Prevalence Survey (PPS) was undertaken in seven tertiary care health facilities in Punjab Provence, Pakistan. Baseline information about antimicrobial use according to the World Health Organization (WHO) standardized methodology was collected on a single day between 5(th) and 30 April 2021. A total of 617 patients’ records were reviewed and 578 (97.3%) were documented to be receiving an antibiotic on the day of the survey. The majority (84.9%) were COVID-19 PCR positive, 61.1% were male and 34.9% were age 36 to 44 years. One quarter presented with severe disease, and cardiovascular disease was the major comorbidity in 13%. Secondary bacterial infection or co-infection (bacterial infection concurrent with COVID-19) was identified in only 1.4%. On the day of the survey, a mean of 1.7 antibiotics was prescribed per patient and 85.4% antibiotics were recorded as being prescribed for ‘prophylaxis’. The most frequently prescribed antibiotics were azithromycin (35.6%), ceftriaxone (32.9%) and meropenem (7.6%). The majority (96.3%) of the antibiotics were empirical and all were from WHO Watch or Reserve categories. Overall, a very high consumption of antibiotics in patients hospitalized with suspected or proven COVID-19 was observed in Pakistan and this is concerning in view of already high rates of antimicrobial resistance in the region. Antimicrobial stewardship programs need to urgently address unnecessary prescribing in the context of COVID-19 infection.

Respiratory Viral infections predispose patients to various coinfections and this may lead to enhanced disease severity and mortality. Despite the proven importance of co-infections, these are understudied during the large outbreaks of respiratory infections. Occurrence of invasive fungal respiratory superinfections in patients with COVID-19 has gained increasing attention recently. This study aims to assess Clinical & Microbiological profile of patients with invasive sinusitis in setting of COVID-19 disease at our institute Study Design: A retrospective observational study. Study included patients diagnosed with acute invasive fungal rhinosinusitis (AIFR) suffering from or having a history of coronavirus disease infection over the period of three months.(April 21 – June 21). The patients’ presentation details, imaging findings, co-morbidities, management details, and follow-up information were obtained, recorded and analysed. A total of 32 patients with AIFR with a mean age of 54.46±13.13 years old were included. Most common associated disease was diabetes mellitus (62.5%). Mycological analysis revealed most common fungi isolated from these patients were Mucor species.(56.25%) followed by Aspergillus species(15.62%) while coinfection with both of these species was seen in 5 patients.(15.62%) Candida species was isolated from samples of 4 patients (12.5%). Radiological studies of nose and paranasal sinuses showed that ethmoid (62.5%) and maxillary (46.87%) sinuses being the most commonly affected sinuses followed by Frontal (31.25%) and sphenoid (21.87%) sinuses. Peri-orbital invasion was seen in 5 (15.62%) cases whereas intracranial involvement was seen in 1 patient.(3.12%) In 8 (25%) patients only medical line of treatment was sufficient whereas 20 (62.5%) patients required surgical debridement during the treatment. 4 patients were lost to follow up. Overall survival was 90.62% (29/32) at the conclusion of the study. We are still learning the new and long-term complications of COVID- 19.The puzzle still remains unsolved about the cause and increased prevalence of invasive fungal infections in post-covid-19 population. High clinical suspicion and early and accurate diagnosis of AIFR in COVID-19 patients are essential for better prognosis.

Hepatitis D virus (HDV) is a defective liver-tropic virus that needs the helper function of hepatitis B virus (HBV) to infect humans and replicate. HDV is transmitted sexually or by a parenteral route, in co-infection with HBV or by super-infection in HBV chronic carriers. HDV infection causes acute hepatitis that may progress to a fulminant form (7%-14% by super-infection and 2%-3% by HBV/HDV co-infection) or to chronic hepatitis (90% by HDV super-infection and 2%-5% by HBV/HDV co-infection), frequently and rapidly progressing to cirrhosis or hepatocellular carcinoma (HCC). Peg-interferon alfa the only recommended therapy, clears HDV in only 10%-20% of cases and, consequently, new treatment strategies are being explored. HDV endemicity progressively decreased over the 50 years from the identification of the virus, due to improved population lifestyles and economic levels, to the use of HBV nuclei(t)side analogues to suppress HBV replication and to the application of universal HBV vaccination programs. Further changes are expected during the severe acute respiratory syndrome coronavirus-2 pandemic, unfortunately towards increased endemicity due to the focus of healthcare towards coronavirus disease 2019 and the consequently lower possibility of screening and access to treatments, lower care for patients with severe liver diseases and a reduced impulse to the HBV vaccination policy.

Mucormycosis is an angioinvasive infection caused by fungi Mucorales which mainly occurs in immunocompromised patients. Aspergillosis is also an opportunistic fungal infection caused by Aspergillus species. Coinfection with mucormycosis and aspergillosis is very rare and very few cases were published in the literature till now. There is an increase in the incidence of mucormycosis infection in post-COVID-19 patients. Here, we are going to report a case series of three cases of combined infection of mucormycosis with Aspergillus. All three patients were treated with extensive surgical debridement and intravenous liposomal amphotericin B. Even after aggressive treatment, the mortality rate is high in these types of patients.

OBJECTIVE Persons living with HIV (PLWH) and co-infected with hepatitis C (PLWH + HCV) have increased risk of cardiovascular disease (CVD). Peri-coronary inflammation, measured by fat attenuation index (FAI) on coronary CT angiography (CCTA), independently predicts cardiovascular risk in the general population but has not been studied in the PLWH + HCV population. We tested whether peri-coronary inflammation is increased in PLWH or PLWH + HCV, and whether inflammation changes over time. DESIGN Cross-sectional analysis to determine FAI differences among groups. Longitudinal analysis in PLWH to assess changes in inflammation over time. METHODS Age- and sex-matched seropositive groups (PLWH and PLWH + HCV) virologically suppressed on antiretroviral therapy (ART), HCV viremic, and without prior CVD and matched controls underwent CCTA. Peri-coronary FAI was measured around the proximal right coronary artery (RCA) and left anterior descending artery (LAD). Follow-up CCTA was performed in 22 PLWH after 20.6-27.4 months. RESULTS 101 participants (48 women) were studied (60 PLWH, 19 PLWH + HCV and 22 controls). In adjusted analyses, peri-coronary FAI did not differ between seropositive groups and controls. Low attenuation coronary plaque was significantly less common in seropositive groups compared to controls (LAD, p = 0.035; and RCA, p = 0.017, respectively). Peri-coronary FAI values significantly progressed between baseline and follow-up in PLWH (RCA: p = 0.001, LAD: p =

The objective of the study: to study the possibilities of skin tests with tuberculosis recombinant allergen (TRA) in the diagnosis of tuberculosis in HIV-positive patients in the region with a high prevalence of tuberculosis.Subjects and Methods. Medical files of 85 patients were retrospectively analyzed, all the patients suffered from TB/HIV coinfection and underwent the skin test with TRA.Results. The skin test with TRA was found to be significantly valuable for the diagnosis of tuberculosis in patients with TB/HIV coinfection. The correlation between the intensity of response to the TRA test and CD4+ count was detected (p = 0.011). The lowest values were observed for CD4+ counts below 100 cells/μL. The direct correlation between the intensity of response to TRA and the stage of HIV infection was proved. No effect of the form of tuberculosis, the phase of the tuberculosis disease, or drug sensitivity on the intensity of response to TRA was found. Among tuberculosis patients with bacterial excretion (n = 48), 68.8% of patients responded positively to the TRA test, and in those with no bacterial excretion, the positive reaction was observed in 81.1%.

PURPOSE The objective of this study was to compare the clinical and microbiological profiles of culture-proven pure Corynebacterium keratitis with mixed infection and their antibiotic susceptibility patterns over a 2-year period. METHODS A retrospective analysis of culture-proven cases of Corynebacterium keratitis over a 2-year period was performed in 3 different tertiary eye care centers. All isolates were tested for antibiotic susceptibility in vitro using the disc-diffusion method for 7 antibiotics. RESULTS Altogether 108 cases were identified as culture-positive Corynebacterium keratitis in 3 tertiary eye care centers. Of these, 60.2% (n = 65) and 39.8% (n = 43) of cases were due to pure Corynebacterium and mixed infection, respectively. The mean duration of symptoms was 23.2 ± 29.6 days. In the mixed-infection group, fungus was identified as the coexistent pathogen in 22 cases (51.1%). Ocular surface disorder was the most common risk factor (33.9%) in Corynebacterium keratitis. The most frequently isolated species was Corynebacterium amycolatum (22.2%) in both groups. Therapeutic keratoplasty was performed in 8.3% of cases. There was no significant difference in the outcome between the 2 groups. Cefazolin resistance was seen in 13.9% of patients, and all isolates were susceptible to vancomycin. The resistance pattern showed emerging resistance toward fluoroquinolone because the isolates were resistant to gatifloxacin (58.3%), moxifloxacin (47.2%), ciprofloxacin (54.6%), and ofloxacin (45.4%). CONCLUSIONS Ocular surface disorder is the most common risk factor in Corynebacterium keratitis. Although fluoroquinolones are commonly used as first-line therapy in microbial keratitis, the in vitro resistance pattern indicates that these are less likely to be effective in infection with Corynebacterium species.

Objectives Gonococcal infections with a higher bacterial load may pose a higher risk of transmission. We assessed the association between gonococcal bacterial load and coinfection with Mycoplasma genitalium. Methods From September 2015 until May 2018, 200 men and transgender women who have sex with men participated in an HIV pre-exposure prophylaxis (PrEP) demonstration trial in Antwerp, Belgium. They underwent 3-monthly 3-site (anus, urine, and pharynx) molecular testing for N. gonorrhoeae and C. trachomatis and M. genitalium, irrespective of symptoms. Gonococcal bacterial load was determined on remnant DNA extracts using an in-house quantitative PCR. Results were expressed as log10 transformed copies/mL and analyzed with a linear regression model. Results Gonococcal bacterial load could be determined for 82 (80.4%) of 102 anal, 17 (73.9%) of 23 urine, and 64 (90.1%) of 71 pharyngeal samples. M. genitalium was detected in five of these anal, two urine, and two pharyngeal samples and C. trachomatis was detected in 16 anal, one urine, and two pharyngeal samples. Gonococcal bacterial load was significantly higher in the presence of M. genitalium (difference 0.92 log copies/mL, 95% CI 0.16–1.67). Conclusions Gonococcal bacterial load was higher with M. genitalium coinfection. M. genitalium may thus be a cofactor in gonococcal transmission.

The objective of the study: to summarize experience of using a mobile technology to improve adherence in patients with tuberculosis and HIV infection (TB/HIV) who are psychoactive substance users.Subjects and Methods. A smartphone app was used, it included daily patient inquiries about mood, stress levels, and medication intake; periodic reminders about outpatient appointments; and anonymous chats with the coordinating physician and other patients. Treatment results were evaluated in Group 1 (n = 54) and Group 2 (n = 50), where this technology was used and not used, respectively.Results. The number of patients cured of tuberculosis was not significantly different between Groups 1 and 2 (32/51 vs. 27/48; χ2 = 0.61, p = 0.48). Patients from Group 2 died significantly more often during the follow-up period (14/48 vs. 3/51; χ2 = 7.86, p = 0.006) associated with antiretroviral therapy interruption or withdrawal. Increased CD4 count by 6 months of follow-up was found in both groups, most pronounced among those who started ART (W = 6.0, p = 0.004 – in Group 1 and W = 15.0, p = 0.004 – in Group 2). The total number of patients with viral suppression was greater in Group 1 than in Group 2 (34/47 vs. 20/39; χ2 = 4.05, p = 0.04).Conclusion. The mobile app used is suitable for supporting the outpatient management of patients with TB/HIV coinfection but its direct impact was reflected only in the formation of ART adherence and lower number of deaths.

We describe a March 2020 co-occurrence of Legionnaires' disease (LD) and coronavirus disease in France. Severe acute respiratory syndrome coronavirus 2 co-infections were identified in 7 of 49 patients from LD case notifications. Most were elderly men with underlying conditions who had contracted severe pneumonia, illustrating the relevance of co-infection screening.

The geographical overlaps of malaria parasites and Salmonella spp. can lead to co-infection of these two pathogens, especially in the tropics where malaria is endemic. Moreover, few literatures suggested that malaria infection was associated with Salmonella bacteremia. Therefore, this study quantified pooled prevalence of typhoidal/non-typhoidal Salmonella (NTS) and probability of typhoidal/NTS and malaria co-infection among febrile patients. The systematic review protocol was registered at PROSPERO (CRD42021252322). Studies on co-infection of typhoidal/NTS and malaria were searched in PubMed, Scopus, and Web of Science. The risk of bias of the included studies was assessed using the checklist for analytical cross-sectional studies developed by the Joanna Briggs Institute. Meta-analyses on the following criteria were performed: (1) pooled prevalence of typhoidal/NTS and malaria co-infection among febrile patients, (2) pooled prevalence of typhoidal/NTS among malaria patients, (3) pooled prevalence of malaria infections among patients with Salmonella spp. infection, and (4) probability of typhoidal/NTS and malaria co-infection among febrile patients. Additionally, the case fatality rate and mean difference of malarial parasitemia between typhoidal/NTS and malaria co-infection and Plasmodium monoinfection were also determined. The subgroup analyses of typhoidal/NTS, regions (Africa and Asia), countries, time (publication year), characteristics of participants, and diagnostic tests for identifying Salmonella spp. were also conducted. A sensitivity test was performed to determine the robustness of the study outcomes. Publication bias among the included studies was evaluated using the funnel plot and Egger’s test. All analyses were performed using Stata version 15 (StataCorp LLC, Texas, USA) with a p-value 2, 99.4%; 2971/17,720 cases) and 1% (95% CI 1–1%; I2, 89.9%; 252/29,081 cases) using the Widal test and culture methods for identifying Salmonella spp., respectively. The pooled prevalence rates of typhoidal/NTS infection among patients with malaria were 31% (95% CI 23–39%; I2, 99.5%; 3202/19,208 cases) and 3% (95% CI 2–3%; I2, 86.8%; 407/40,426 cases) using the Widal test and culture methods for identifying Salmonella spp., respectively. The pooled prevalence rates of malaria infection among patients with typhoidal/NTS were 17% (95% CI 6–29%; I2, 33.3%; 13/75 cases) and 43% (95% CI 32–53%; I2, 89.1%; 287/736 cases), respectively. Malaria infection was associated with typhoidal/NTS in children aged 2, 73.9%; 3188/43,212 cases). The case fatality rate in patients with malaria and NTS co-infections was 16% (95% CI 9–24%; I2, 89.1%; 18/103 cases). From the view of the present study, the inappropriate use of the Widal test for Salmonella spp. diagnosis can overestimate the prevalence of typhoidal/NTS and malaria co-infections. Malaria infection associated with typhoidal/NTS in children and the high case fatality rates among few patients with co-infections were highlighted. Future prospective longitudinal studies using the appropriate and confirmatory dsiagnosis for Salmonella spp. infections are highly recommended to ensure the real prevalence of co-infection and highlight the outcome of co-infection for providing adequate treatment in febrile patients who live in areas where malaria is endemic, such as tropical Africa and India.

Bei Li,1 Leidan Zhang,2 Ying Liu,1 Jing Xiao,2 Xinyue Wang,2 Yuqing Wei,1 Lina Fan,3 Yujiao Duan,1 Guoli Li,4 Yaxian Kong,4 Hongxin Zhao1 1Clinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Infection, Beijing Ditan Hospital, Peking University, Beijing, People’s Republic of China; 3Department of Infectious Disease, The Tianjin Second People’s Hospital, Tianjin, People’s Republic of China; 4Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Hongxin ZhaoClinical and Research Center of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, No. 8 Jing Shun East Street, Beijing, 100015, People’s Republic of ChinaEmail Drzhao66@ccmu.edu.cnBackground: At present, the thrombocyte abnormality is not well described before and after the initiation of antiretroviral therapy (ART). The purpose of this research is to investigate the dynamic changes and related risk factors of thrombocytopenia and thrombocytosis in HIV-infected individuals.Methods: We performed a real-world observational study among 6637 HIV patients who started ART from January, 2013 to August, 2020 at the Beijing Ditan Hospital. Hazard indicators linked with thrombocytopenia and thrombocytosis were analyzed by logistic/Cox regression.Results: The prevalence of thrombocytopenia and thrombocytosis was 2.65% and 5.85% among ART-naïve patients, respectively. Correlated risk factors: (thrombocytopenia) older age, coinfection with HBV, leucopenia, anemia, and CD4 count < 350 cells/uL; (thrombocytosis) WBC level ≥ 4.0 x 109/L, anemia, NLR ≥ 2.0, and CD4 count ≥ 350 cells/uL. As for the recovery rate, it was 86.6/54.2, 83.4/46.3, 66.0/35.1, and 65.3/ 33.9 per 100 PYFU in thrombocytopenia/thrombocytosis at different treatment period (12m, 24m, 36m, and 48m). While the new-onset incidence of thrombocytopenia/thrombocytosis at different ART period (12m, 24m, 36m, 48m, 60m, 72m, and 84m) was 0.25/7.2, 0.19/6.31, 0.16/4.74, 0.16/4.55, 0.16/4.48, 0.15/4.41, and 0.15/4.39. And the driving forces of thrombocytosis were antiretroviral treatment, female, overweight, and WBC level ≥ 4.0 x 109/L.Conclusion: In the medical practice, while paying attention to thrombocytopenia, clinicians should be highly vigilant about the thrombocytosis of HIV/AIDS patients, and related treatment strategies need to be further studied.Keywords: thrombocyte abnormalities, thrombocytopenia, thrombocytosis, HIV, antiretroviral therapy

Candida utilis and Stenotrophomonas maltophilia co-infections connected to meningitis are uncommon. We describe a patient who developed C. utilis and S. maltophilia after undergoing neurosurgery and received effective nosocomial meningitis treatment. Multiple neurosurgeries were required for a 16-year-old girl due to complications. For probable nosocomial meningitis, she was treated with cefepime with vancomycin. Meropenem and liposomal amphotericin B were prescribed after her seizure and positive CSF culture for Candida utilis. Consequently, S. maltophilia was discovered in the CSF, and ceftazidime and trimethoprim-sulfamethoxazole were prescribed. The patient has been hemodynamically stable for the past two months, and consecutive CSF cultures have been negative. To the best of our knowledge, this is the first case of C. utilis and S. maltophilia co-infection that has been successfully handled.

Background Anal squamous intraepithelial lesions (ASIL), strongly related to human papilloma virus (HPV) infection, is more prevalent among men who have sex with men (MSM). However, no such data are available for Pakistan yet, and neither HPV vaccination nor anal-cytology screening is implemented in Pakistan. The purpose of this first ever study was to assess the prevalence of HPV-related anal cytological abnormalities among MSM and transgender women living with and without HIV infection in Pakistan. Methods We conducted a cross-sectional study from March 2016 to November 2017 at sexual health centers run by the Perwaaz Trust and the National AIDS Control Program in Karachi. The study enrolled MSM and transgender women aged greater-than-and-equal-to-18-years who reported anal sex in the preceding 6 months. We collected two anal samples for liquid-based cytology and HPV type testing by PCR, and socio-demographic and behavioral data were collected through face-to face interviews. ASIL and its associations with biological and behavioral risk factors were analyzed through Cox regression for prevalence ratios (PR) and corresponding 95% confidence intervals (CIs). Results Out of 271 qualifying participants, 79% were MSM and 21% transgender women. The mean age was 28.8 (± 8) years. Almost 35% (93/271) of the study population had ASIL detected, ASIL was significantly more common among participants living with HIV than in HIV negative ((50/118) 42.4%; vs. (43/153) 28.1%) (p ≤ 0.001). Among ASIL, 66% (61/93) had low-grade squamous intraepithelial lesions (LSIL), and 3.6% (3/93) had high-grade squamous intraepithelial lesions (HSIL). The overall, HPV16 positivity was 35.5% (33/93) among all abnormal anal lesions and all 3 HSIL were HPV16 positive, however, HPV16 positivity could show its association with ASIL detection in univariate model only (PRcrude: 2.11(1.39–3.18)). Moreover, any HR-HPV type (PR 3.04; 95% CI 1.75–5.26), concurrent sexually transmitted infection (STI) (2.13; (1.28–3.55)) and HIV + /HPV + coinfection (1.75; (1.07–2.88)) remained independently associated with ASIL in the multivariate model. Conclusions Abnormal anal cytology among MSM and transgender is prevalent enough to consider optimal screening regimens. Further studies are required to see if periodic anal cytology can be made part of HIV care and treatment programs among MSM in Pakistan.

A reproducible animal model is required to study the pathophysiology of wound infections and for development of effective therapeutic interventions. The objective of this study was to produce an infected skin wound model utilizing the cecal microbiota in non-immunocompromised rats.An excision wound was created on the dorsal surface of rats and inoculated with different concentration of cecal slurry (CS). Wound progression was investigated macroscopically by wound scoring and imaging. The rats were sacrificed on day 6 and microbial load, myeloperoxidase activity, histopathology, and scanning electron microscopy (SEM) were performed in wound tissue.Inoculation of CS into excision wounds caused significantly (p0.05) delayed wound healing in comparison to non-infected wounds as revealed by slow wound closure (9.1 to 12.83%). A significant (p0.05) difference in wound score was observed between the infected and non-infected wounds. A significantly (p0.05) high microbial load (~10The study reports a reproducible and relevant clinical model of wound infection where cecal microbiota was used as a source of infection. This model can provide a suitable platform for evaluation of new therapeutic interventions.

BACKGROUND Previous studies have shown substantial differences in geographic clustering of sexually transmitted infections (STI), such as chlamydia (CT) and gonorrhea (NG), conditional on epidemic phase. Chlamydia and NG have recently shown resurgent epidemiology in the northern hemisphere. This study describes the recent epidemiology of CT and NG in Winnipeg, Canada, combining traditional surveillance tools with place-based analyses, and comparing the ecological niches of CT and NG, in the context of their evolving epidemiology. METHODS Data were collected as part of routine public health surveillance between 2007 and 2016. Secular trends for CT and NG, and CT/NG coinfection were examined. Gini coefficients and population attributable fractions explored the distribution, and concentration of infections over time and space. RESULTS Rates of CT increased from 394.9/100,000 population to 476.2/100,000 population from 2007 to 2016. Gonorrhea rates increased from 78.0/100,000 population to 143.5/100,000 population during the same period. Each pathogen had its own ecological niche: CT was widespread geographically and socio-demographically, while NG was clustered in Winnipeg's inner-core. CT/NG co-infections had the narrowest space and age distribution. NG was shown to be undergoing a growth phase, with clear signs of geographic dispersion. The expansion of NG resembled the geographic distribution of CT. CONCLUSIONS We demonstrated that NG was experiencing a growth phase, confirming theoretical predictions of geographic dispersion during a growth phase. During this phase, NG occupied similar geographic spaces as CT. Knowledge of different ecological niches could lead to better targeting of resources for subpopulations vulnerable to STIs.

Background Antibiotic and antiviral agents may be prescribed in patients with suspected or confirmed coronavirus disease 2019 (COVID-19) infections because of in vitro evidence of cessation of viral replication, potential bacterial secondary or coinfection, and inability to distinguish COVID-19 infections from common bacterial infections. The objective of this study was to evaluate antimicrobial prescribing patterns in the outpatient setting during the initial peak of COVID-19 in New York City. Methods This single-center, retrospective chart review included patients at least 18 years old who were prescribed oral antimicrobial agents in outpatient primary care clinics between March and May 2020. Data were compared with prescribing patterns from March to May 2019. The primary outcome was the number of antimicrobial prescriptions per 1000 patient visits. Secondary outcomes included documented indication, incidence of confirmed infections, mortality, and/or hospital admission within 90 days. Descriptive statistics were used. Results The overall antimicrobial prescribing rate increased from 31.94 prescriptions per 1000 visits in 2019 to 57.48 prescriptions per 1000 visits in 2020. Agents that were more commonly prescribed during the initial peak of COVID-19 include cefpodoxime, hydroxychloroquine, doxycycline, and sulfamethoxazole-trimethoprim. COVID-19 represented 7 (6%) documented antimicrobial indications in 2020, with agents such as azithromycin, hydroxychloroquine, doxycycline, cefpodoxime, and oseltamivir prescribed. Conclusions Overall antimicrobial prescribing rates in outpatient primary care clinics increased during the first peak of COVID-19 in an area with high infection burden. This increase may have been influenced by restricted patient evaluation, changes in patient management, and a decrease in overall patient visits.

Summary Pneumonia in cats may cause severe lung injury and consequent death. We describe the post-mortem findings and aetiologies of naturally fatal pneumonia in 78 domestic cats, using gross and histopathological examinations, immunohistochemistry and microbiological techniques. Morphological patterns found were bronchopneumonia (27/78), interstitial (15/78), bronchointerstitial (13/78), granulomatous (8/78), aspiration (8/78) and pyogranulomatous (5/78) pneumonia, and pleuropneumonia (2/78). Bacterial pneumonia was identified as the most common cause (32/78), followed by viral (15/28 feline calicivirus, 10/28 felid alphaherpesvirus 1 and 3/28 both viruses), aspiration (8/78), fungal (5/78) and parasitic pneumonia (5/78). Co-infection with feline immunodeficiency virus and feline leukaemia virus was found in 54 cats. Viral infections involved cats of all ages, indicating the importance of investigating viral causes in cats with respiratory diseases, including in adult and ageing cats.

Introduction: Human T-lymphotropic virus (HTLV) 1 and 2 infections can lead to neurological diseases, mainly in HIV/HTLV 1 coinfected. Furthermore, HTLV 1 infection in HIV/AIDS patients has also been associated with AIDS progression. Despite this, HTLV 1/2 infections are not of mandatory notification in Brazil. Here, we describe the prevalence of HTLV 1/2 in HIV/AIDS patients from Paraíba state, Brazil, as well as the sociodemographic characteristics of the coinfected individuals. Methodology: Information about HIV viral load and TCD4 lymphocyte count were obtained from patients’ records. Data on the patients’ sociodemographic characteristics were obtained by interview conducted after signing the informed consent form. The serological diagnosis for HTLV 1/2 was performed by Enzyme-Linked Immunosorbent Assay (ELISA) and Western Blot (WB). Results: A total of 401 HIV/AIDS patients participated in the study, of whom about 1.5% (6/401) were positive for antibodies against HTLV, specifically for HTLV 1, evaluated by both ELISA and WB. No risk factors were found associated with HIV/HTLV 1/2 coinfection. Conclusions: We report a 1.5% prevalence of HTLV 1 infection in HIV/AIDS patients from Paraíba state. Although we have not identified risk factors associated with HTLV 1, we describe the most observed sociodemographic characteristics in HIV/HTLV 1 coinfection.

Background Although COVID-19 is associated with a mild course in children, a certain proportion requires admission to hospital due to SARS-CoV-2 infection and coexisting diseases. The prospective multicenter study aimed to analyze clinical factors influencing the length of the hospital stay (LoHS) in children with COVID-19. Methods The study included 1283 children from 14 paediatric infectious diseases departments with diagnosed SARS-CoV-2 infection. Children were assessed in respective centres regarding indications for admission to hospital and clinical condition. History data, clinical findings, laboratory parameters, treatment, and outcome, were collected in the paediatric SARSTer register. The group of children with a hospital stays longer than seven days was compared to the remaining patients. Parameters with a statistically significant difference were included in further logistic regression analysis. Results One thousand one hundred and ten children were admitted to the hospital, 763 children were hospitalized >24 h and 173 children >7 days. 268 children had comorbidities. Two hundred and eleven children had an additional diagnosis with coinfections present in 135 children (11%). Factors increasing the risk of higher LoHS included pneumonia [odds ratio—OR 3.028; 95% confidence interval—CI (1.878–4.884)], gastrointestinal symptoms [OR = 1.556; 95%CI (1.049–2.322)], or rash [OR = 2.318; 95%CI (1.216–4.418)] in initial clinical findings. Comorbidities [OR = 2.433; 95%CI (1.662–3.563)], an additional diagnosis [OR = 2.594; 95%CI (1.679–4.007)] and the necessity of the empirical antibiotic treatment [OR = 2.834; 95%CI (2.834–6.713)] were further factors related to higher LoHS. Conclusions The clinical course of COVID-19 was mild to moderate in most children. Factors increasing the risk of higher LoHS included pneumonia, gastrointestinal symptoms, comorbidities, an additional diagnosis, and the empirical antibiotic treatment.