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•The majority of sexually active individuals becomes infected with HPV at least once.•Little is known about prevalence rates and determinants of oral HPV infection.•Transmission to oral cavity and pharynx probably occurs through sexual contact.•Exposure of oropharyngeal mucosa to HPV depends on specific sexual behavior.•Specific high-risk groups for any prevalent oral HPV infection can be identified. This review focuses on the importance of oral and laryngeal HPV infection which is present in majority of sexually active individuals at least once in their lifetime. Despite testing, still little is known about prevalence rates, determinants and, especially, the concurrent HPV infection in head and neck, and genitals. The purpose of this review is to clarify some issues of oral HPV incidence, prevalence, and to demonstrate the difficulties in identification of asymptomatic oral HPV carriers. The main premise to take up this topic is the high and still increasing risk for development of oropharyngeal cancer, and potential benefit from screening strategies, education programs and HPV vaccination. Transmission of HPV to the oral cavity and oropharynx is hypothesized to occur mainly through sexual contact. The exposure of oropharyngeal mucosa to HPV infection with consequence of increased risk for oropharyngeal carcinoma depends on specific sexual behavior. Male gender, older age, race or ethnicity, oral hygiene and current cigarette smoking are independently associated with any prevalent oral HPV infection.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel β-coronavirus, is the main pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects much more people, especially the elder population, around the world than other coronavirus, such as SARS-CoV and MERS-CoV, which is challenging current global public health system. Beyond the pathogenesis of SARS-CoV-2, microbial coinfection plays an important role in the occurrence and development of SARS-CoV-2 infection by raising the difficulties of diagnosis, treatment, prognosis of COVID-19, and even increasing the disease symptom and mortality. We summarize the coinfection of virus, bacteria and fungi with SARS-CoV-2, their effects on COVID-19, the reasons of coinfection, and the diagnosis to emphasize the importance of microbial coinfection in COVID-19.Key points• Microbial coinfection is a nonnegligible factor in COVID-19.• Microbial coinfection exacerbates the processes of the occurrence, development and prognosis of COVID-19, and the difficulties of clinical diagnosis and treatment.• Different virus, bacteria, and fungi contributed to the coinfection with SARS-CoV-2.

Bacterial and fungal co-infection has been reported in patients with COVID-19, but there is limited experience on these infections in critically ill patients. The objective of this study was to assess the characteristics and ouctome of ICU-acquired infections in COVID-19 patients. We conducted a retrospective single-centre, case-control study including 140 patients with severe COVID-19 admitted to the ICU between March and May 2020. We evaluated the epidemiological, clinical, and microbiological features, and outcome of ICU-acquired infections. Fifty-seven patients (40.7%) developed a bacterial or fungal nosocomial infection during ICU stay. Infection occurred after a median of 9 days (IQR 5–11) of admission and was significantly associated with the APACHE II score (p = 0.02). There were 91 episodes of infection: primary (31%) and catheter-related (25%) bloodstream infections were the most frequent, followed by pneumonia (23%), tracheobronchitis (10%), and urinary tract infection (8%) that were produced by a wide spectrum of Gram-positive (55%) and Gram-negative bacteria (30%) as well as fungi (15%). In 60% of cases, infection was associated with septic shock and a significant increase in SOFA score. Overall ICU mortality was 36% (51/140). Infection was significantly associated with death (OR 2.7, 95% CI 1.2–5.9, p = 0.015) and a longer ICU stay (p < 0.001). Bacterial and fungal nosocomial infection is a common complication of ICU admission in patients with COVID-19. It usually presents as a severe form of infection, and it is associated with a high mortality and longer course of ICU stay.

Tuberculosis remains a global health challenge, with early diagnosis key to its reduction. Face-mask sampling detects exhaled Mycobacterium tuberculosis. We aimed to investigate bacillary output from patients with pulmonary tuberculosis and to assess the potential of face-mask sampling as a diagnostic method in active case-finding. We did a 24-h longitudinal study in patients from three hospitals in Pretoria, South Africa, with microbiologically confirmed pulmonary tuberculosis. Patients underwent 1 h of face-mask sampling eight times over a 24-h period, with contemporaneous sputum sampling. M tuberculosis was detected by quantitative PCR. We also did an active case-finding pilot study in inhabitants of an informal settlement near Pretoria. We enrolled individuals with symptoms of tuberculosis on the WHO screening questionnaire. Participants provided sputum and face-mask samples that were tested with the molecular assay Xpert MTB/RIF Ultra. Sputum-negative and face-mask-positive individuals were followed up prospectively for 20 weeks by bronchoscopy, PET-CT, and further sputum analysis to validate the diagnosis. Between Sept 22, 2015, and Dec 3, 2015, 78 patients with pulmonary tuberculosis were screened for the longitudinal study, of whom 24 completed the study (20 had HIV co-infection). M tuberculosis was detected in 166 (86%) of 192 face-mask samples and 38 (21%) of 184 assessable sputum samples obtained over a 24-h period. Exhaled M tuberculosis output showed no diurnal pattern and did not associate with cough frequency, sputum bacillary content, or chest radiographic disease severity. On May 16, 2018, 45 individuals were screened for the prospective active case-finding pilot study, of whom 20 had tuberculosis symptoms and were willing to take part. Eight participants were diagnosed prospectively with pulmonary tuberculosis, of whom six were exclusively face-mask positive at screening. Four of these participants (three of whom were HIV-positive) had normal findings on chest radiography but had treatment-responsive early tuberculosis-compatible lesions on PET-CT scans, with Xpert-positive sputum samples after 6 weeks. Face-mask sampling offers a highly efficient and non-invasive method for detecting exhaled M tuberculosis, informing the presence of active infection both with greater consistency and at an earlier disease stage than with sputum samples. The approach shows potential for diagnosis and screening, particularly in difficult-to-reach communities. Wellcome Trust, CARA (Council for At-Risk Academics), University of Leicester, the UK Medical Research Council, and the National Institute for Health Research. [Display omitted]

Gut microbiota has been demonstrated to be involved in intestinal nutrition, defense, and immunity, as well as participating in disease progression. This study was to investigate gut microbiota changes in chickens challenged with netB-positive Clostridium perfringens strain (CP1) and/or the predisposing Eimeria species (Eimeria) and fed diets with fishmeal supplementation. In addition, the effects of lauric acid, a medium-chain fatty acid (MCFA), on necrotic enteritis (NE) reduction and modulation of microbiota were evaluated. The results demonstrated that microbial communities in the jejunum were distinct from those in the cecum, and the microbial community change was more significant in jejunum. Challenge of CP1 in conjunction with Eimeria significantly reduced species diversity in jejunal microbiota, but cecal microbiota remained stable. In the jejunum, CP1 challenge increased the abundance of the genera of Clostridium sensu stricto 1, Escherichia Shigella, and Weissella, but significantly decreased the population of Lactobacillus. Eimeria infection on its own was unable to promote NE, demonstrating decrements of Clostridium sensu stricto 1 and Lactobacillus. Co-infection with CP1 and Eimeria reproduced the majority of NE lesions with significant increment of Clostridium sensu stricto 1 and reduction in Lactobacillus. The advance of changes on these two taxa increased the severity of NE lesions. Further analyses of metagenomeSeq, STAMP, and LEfSe consistently showed significant overgrowth of Clostridium sensu stricto 1 was associated with NE. The supplementation of lauric acid did not reduce NE incidence and severity but decreased the relative abundance of Escherichia Shigella. In conclusion, significant overgrowth of C. perfringens as well as other Clostridium species in Clostridium sensu stricto 1 with the decrement of Lactobacillus in the jejunum is the featured microbiota correlated with NE. Controlling proliferation of Clostridium sensu stricto 1 and manipulation of Lactobacillus in the jejunum should be the strategy to prevent NE.

Parasitic helminth infections have a considerable impact on global human health as well as animal welfare and production. Although co-infection with multiple parasite species within a host is common, there is a dearth of tools with which to study the composition of these complex parasite communities. Helminth species vary in their pathogenicity, epidemiology and drug sensitivity and the interactions that occur between co-infecting species and their hosts are poorly understood. We describe the first application of deep amplicon sequencing to study parasitic nematode communities as well as introduce the concept of the gastro-intestinal \"nemabiome\". The approach is analogous to 16S rDNA deep sequencing used to explore microbial communities, but utilizes the nematode ITS-2 rDNA locus instead. Gastro-intestinal parasites of cattle were used to develop the concept, as this host has many well-defined gastro-intestinal nematode species that commonly occur as complex co-infections. Further, the availability of pure mono-parasite populations from experimentally infected cattle allowed us to prepare mock parasite communities to determine, and correct for, species representation biases in the sequence data. We demonstrate that, once these biases have been corrected, accurate relative quantitation of gastro-intestinal parasitic nematode communities in cattle fecal samples can be achieved. We have validated the accuracy of the method applied to field-samples by comparing the results of detailed morphological examination of L3 larvae populations with those of the sequencing assay. The results illustrate the insights that can be gained into the species composition of parasite communities, using grazing cattle in the mid-west USA as an example. However, both the technical approach and the concept of the 'nemabiome' have a wide range of potential applications in human and veterinary medicine. These include investigations of host-parasite and parasite-parasite interactions during co-infection, parasite epidemiology, parasite ecology and the response of parasite populations to both drug treatments and control programs.

[...]the participating hospitals were either university hospitals (n = 9) or large teaching hospitals (n = 3), and 11 EDs had paediatric intensive care facilities. Collected data included age, sex, season, referral, comorbidity (chronic condition expected to last at least 1 year) [22], triage urgency, fever duration, fever measured at ED, presence of “red traffic light” symptoms for identifying risk of serious illness (alarming signs) (from the National Institute for Health and Care Excellence [NICE] guideline on fever [23]: decreased consciousness, ill appearance, work of breathing, meningeal signs, focal neurology, non-blanching rash, dehydration, status epilepticus), previous antibiotic use, vital signs (heart rate, respiratory rate, oxygen saturation, temperature, capillary refill time), laboratory results (white blood cell count, C-reactive protein [CRP], urinalysis), imaging (chest X-ray and other imaging), microbiological investigations (cultures and respiratory viral tests), and disposition (intensive care unit admission, general ward admission or discharge). The focus of infection was categorised as upper respiratory tract (otitis media, tonsillitis/pharyngitis, other), lower respiratory tract, gastrointestinal tract, urinary tract, skin, musculoskeletal, sepsis, central nervous system, flu-like illness, childhood exanthem, inflammatory syndrome, undifferentiated fever, or other. CRP, C-reactive protein; LRTI, lower respiratory tract infection; URTI, upper respiratory tract infection. *Patients could have identified viral co-infection. https://doi.org/10.1371/journal.pmed.1003208.g001 We aimed to improve data quality and standardised data collection by using a training module for the local clinical and research teams to optimise clinical assessment and data collection for febrile children.

Certain respiratory fungal pathogen mono-infections can cause high mortality rates. Several viral pathogen mono-infections, including influenza viruses and coronaviruses including SARS-CoV-2, can also cause high mortality rates. Concurrent infections by fungal pathogens and highly manipulative viral pathogens can synergistically interact in the respiratory tract to substantially increase their mortality rates. There are at least five viral manipulations which can assist secondary fungal infections. These viral manipulations include the following: (1) inhibiting transcription factors and cytokine expressions, (2) impairing defensive protein expressions, (3) inhibiting defenses by manipulating cellular sensors and signaling pathways, (4) inhibiting defenses by secreting exosomes, and (5) stimulating glucocorticoid synthesis to suppress immune defenses by inhibiting cytokine, chemokine, and adhesion molecule production. The highest mortality respiratory viral pandemics up to now have had substantially boosted mortalities by inducing secondary bacterial pneumonias. However, numerous animal species besides humans are also carriers of endemic infections by viral and multidrug-resistant fungal pathogens. The vast multi-species scope of endemic infection opportunities make it plausible that the pro-fungal manipulations of a respiratory virus can someday evolve to enable a very high mortality rate viral pandemic inducing multidrug-resistant secondary fungal pathogen infections. Since such pandemics can quickly spread world-wide and outrun existing treatments, it would be worthwhile to develop new antifungal treatments well before such a high mortality event occurs.

Most patients with COVID-19 receive antibiotics despite the fact that bacterial co-infections are rare. This can lead to increased complications, including antibacterial resistance. We aim to analyze risk factors for inappropriate antibiotic prescription in these patients and describe possible complications arising from their use. The SEMI-COVID-19 Registry is a multicenter, retrospective patient cohort. Patients with antibiotic were divided into two groups according to appropriate or inappropriate prescription, depending on whether the patient fulfill any criteria for its use. Comparison was made by means of multilevel logistic regression analysis. Possible complications of antibiotic use were also identified. Out of 13,932 patients, 3047 (21.6%) were prescribed no antibiotics, 6116 (43.9%) were appropriately prescribed antibiotics, and 4769 (34.2%) were inappropriately prescribed antibiotics. The following were independent factors of inappropriate prescription: February-March 2020 admission (OR 1.54, 95%CI 1.18-2.00), age (OR 0.98, 95%CI 0.97-0.99), absence of comorbidity (OR 1.43, 95%CI 1.05-1.94), dry cough (OR 2.51, 95%CI 1.94-3.26), fever (OR 1.33, 95%CI 1.13-1.56), dyspnea (OR 1.31, 95%CI 1.04-1.69), flu-like symptoms (OR 2.70, 95%CI 1.75-4.17), and elevated C-reactive protein levels (OR 1.01 for each mg/L increase, 95% CI 1.00-1.01). Adverse drug reactions were more frequent in patients who received ANTIBIOTIC (4.9% vs 2.7%, p < .001). The inappropriate use of antibiotics was very frequent in COVID-19 patients and entailed an increased risk of adverse reactions. It is crucial to define criteria for their use in these patients. Knowledge of the factors associated with inappropriate prescribing can be helpful.

Yield losses caused by fungal pathogens represent a major threat to global food production. One of the most devastating fungal wheat pathogens is Zymoseptoria tritici . Despite the importance of this fungus, the underlying mechanisms of plant–pathogen interactions are poorly understood. Here we present a conceptual framework based on coinfection assays, comparative metabolomics, and microbiome profiling to study the interaction of Z. tritici in susceptible and resistant wheat. We demonstrate that Z. tritici suppresses the production of immune-related metabolites in a susceptible cultivar. Remarkably, this fungus-induced immune suppression spreads within the leaf and even to other leaves, a phenomenon that we term “systemic induced susceptibility”. Using a comparative metabolomics approach, we identify defense-related biosynthetic pathways that are suppressed and induced in susceptible and resistant cultivars, respectively. We show that these fungus-induced changes correlate with changes in the wheat leaf microbiome. Our findings suggest that immune suppression by this hemibiotrophic pathogen impacts specialized plant metabolism, alters its associated microbial communities, and renders wheat vulnerable to further infections. The fungal plant pathogen Zymoseptoria tritici is a major threat to wheat yield. Here Seybold et al. show that Z. tritici can suppress immune responses not only in infected tissue but also on other leaves, a phenomenon termed “systemic induced susceptibility” that is correlated with systemic changes in metabolite accumulation.