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Purpose of review There is unprecedented movement of people across international borders and parasitic infections, previously restricted to endemic regions, are now encountered in nonendemic areas of the world. Recent findings Migrants may import parasitic infections acquired in their countries of origin. Increasingly, clinicians in nonendemic regions are faced with patients with neglected diseases such as Chagas disease, malaria and strongyloidiasis. There are gaps in knowledge among physicians in nonendemic regions, which lead to missed opportunities for preventive strategies and early treatment. Both primary care and infectious disease physicians should have a broad knowledge of common parasitic infections to improve health outcomes and decrease healthcare disparities through early identification and treatment of disease encountered in migrants. Summary Migrant health is still a young field in medicine; clinicians should be aware of diseases seen in migrants, and access both educational and clinical resources, including experts in tropical medicine, in order to reduce health disparities among migrants. Collaboration between primary care and infectious disease/tropical medicine experts should be strengthened.

Purpose of review Substantial progress has been made recently on the development of new therapeutics for cryptosporidiosis, an infection by the protozoan parasite Cryptosporidium that is associated with diarrhea, malnutrition, growth stunting, cognitive deficits, and oral vaccine failure in children living in low-resource settings. Recent findings Various drug discovery approaches have generated promising lead candidates. The repurposed antimycobacterial drug clofazimine was tested in Malawian HIV patients with cryptosporidiosis but was ineffective. Target-based screens identified inhibitors of lysyl-tRNA synthetase, phenylalanyl-tRNA synthetase, methionyl-tRNA synthetase, and calcium-dependent protein kinase 1. Phenotypic screens led to discovery of a phosphatidylinositol 4-kinase inhibitor, the piperazine MMV665917, and the benzoxaborole AN7973. The relationship between pharmacokinetic properties and in-vivo efficacy is gradually emerging. A pathway to clinical trials, regulatory approval, and introduction has been proposed but additional work is needed to strengthen the route. Summary Several lead compounds with potent activity in animal models and a favorable safety profile have been identified. A sustained effort will be required to advance at least one to clinical proof-of-concept studies. The demonstrated risk of resistance indicates multiple candidates should be advanced as potential components of a combination therapy.

Purpose of review To describe the impact of molecular diagnostics on our understanding of the burden and epidemiology of shigellosis in children in low-income and middle-income countries. Recent findings The incorporation of molecular diagnostics has led to a substantial increase in estimates of the burden of shigellosis and have allowed for further resolution of other aspects of Shigella epidemiology, including the clinical characteristics of shigellosis, the association between clinical and subclinical Shigella infection and linear growth shortfalls, protection after natural infection, duration of convalescent shedding, and host determinants of susceptibility. Summary The increased sensitivity and precision afforded by molecular approaches has represented a major advance in our understanding of the epidemiology and burden of shigellosis in the settings of highest importance.

Purpose of review The ubiquitous expression of angiotensin-converting enzyme-2 receptors and its significance as the origin of viral entry have assisted in comprehending the pathophysiology of extrapulmonary manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In this review, we focus on the clinical significance of gastrointestinal manifestations. Recent findings The global pandemic, a result of the widespread implications of SARS-CoV-2, remains a significant burden to current healthcare systems. Fever, dyspnea, and tussive symptoms have primarily been recognized as the most common presenting signs/symptoms. During the past one year our scope of practice has transcended beyond the management of the respiratory system to incorporate other varying systemic manifestations such as anorexia, nausea, vomiting, diarrhea, and abdominal pain. The outcomes reported by recent studies suggest an association between the presence of gastrointestinal symptoms and important clinical factors such as delay in presentation, disease severity, and mortality. Summary We provide a summarization of the most recent in-depth investigations of coronavirus disease 2019 with gastrointestinal manifestations and their conclusions. Although the pathophysiology remains an area of evolving interest, a better understanding of this disease process may allow for early recognition, efficient triage, and improved prognostication for those presenting with gastrointestinal manifestations of SARS-CoV-2.

Purpose of review We have increasing evidence that alterations of the intestinal microbiome have a strong influence on human health. Previous work has demonstrated the association between changes in the microbiome and metabolic risk factors. One related area of interest is the relationship between dysbiosis and nonalcoholic fatty liver disease (NAFLD), as the global prevalence of NAFLD, and its resultant complications, increases. Recent findings In this review, we summarize the hypothesized pathophysiology of dysbiosis-mediated progression of NAFLD, including promotion of an inflammatory intestinal environment, increased intestinal permeability, endogenous ethanol production, short-chain fatty acid production, secondary bile acid metabolism, and choline depletion. We also review potential therapeutic interventions of the microbiome to slow or prevent NAFLD progression, including antibiotics, probiotics, prebiotics, fecal microbiota transplant, and farnesoid × receptor agonism. Summary Much of the evidence supporting dysbiosis-mediated NAFLD progression has been gathered in high-quality animal trials. There remains a need for additional observational and randomized controlled trials in humans to establish causality between the suspected factors and pathogenesis of NAFLD.

Purpose of review Although the epidemiology of Clostridioides difficile has changed, this organism continues to cause significant morbidity and mortality. This review addresses current and future approaches to the diagnosis of C. difficile disease. Recent findings Over the last several years, large prospective studies have confirmed that there is no single optimal test for the diagnosis of C. difficile disease. The pendulum has swung from a focus on rapid molecular diagnosis during the years of the ribotype 027 epidemic, to a call for use of algorithmic approaches that include a test for toxin detection. In addition, diagnostic stewardship has been shown to improve test utilization, especially with molecular methods. Advances in testing include development of ultrasensitive toxin tests and an expansion of biomarkers that may be more C. difficile specific. Microbiome research may be leveraged to inform novel diagnostic approaches based on measurements of volatile and nonvolatile organic compounds in stool. Summary As rates of C. difficile infection decline, emphasis is now on improving test utilization and a quest for improved diagnostic approaches. These approaches may involve implementation of technologies that improve toxin testing, predict patients likely to have disease and/or a severe outcome, and harnessing research on changes in the microbiome to advance metabolomics.

Purpose of review Alarming rates of antibiotic resistance in bacteria and gastrointestinal dysbiosis associated with traditional antimicrobial therapy have led to renewed interests in developing bacteriophages as novel therapeutics. In this review, we highlight some of the recent advances in bacteriophage therapeutic development targeting important enteropathogens of the gastrointestinal tract. Recent findings Bacteriophages are viruses that infect bacteria, either to utilize the bacterial machinery to produce new progeny or stably integrate into the bacterial chromosome to ensure maintenance of the viral genome. With recent advances in synthetic biology and the discovery of CRISPR-Cas systems used by bacteria to protect against bacteriophages, novel molecular applications are taking us beyond the discovery of bacteriophages and toward innovative applications, including the targeting of bacterial virulence factors, the use of temperate bacteriophages, and the production of bacteriophage proteins as antimicrobial agents. These technologies offer promise to target enteropathogens without disrupting the healthy microbiota of the gastrointestinal tract. Moreover, the use of nanoparticle technology and other modifications are helping researchers circumvent the harsh gastrointestinal conditions that could limit the efficacy of bacteriophages against enteric pathogens. Summary This era of discovery and development offers significant potential to modify bacteriophages and overcome the global impact of enteropathogens.

Purpose of review Over the course of the coronavirus disease 2019 (COVID-19) pandemic, it has become clear that the clinical features, epidemiology, and outcomes of COVID-19 are distinct in children relative to adults. In this review, we will present recent pediatric studies informing our current understanding of COVID-19 in children, and review pediatric considerations surrounding disease transmission, currently available therapies, and vaccination. Recent findings Recent studies have shed light on the clinical epidemiology of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children, identifying a high prevalence of asymptomatic and mild infections, with severe COVID-19 infrequently reported. Several adult clinical trials have informed the use of remdesivir, anti-SARS-CoV-2 monoclonal antibodies, dexamethasone, and tocilizumab in the management of COVID-19. Associations between underlying comorbid medical conditions and severe outcomes, as well as transmission dynamics of SARS-CoV-2 in children, are complex and warrant further study. Finally, highly efficacious vaccines are available for adults and adolescents, with pediatric trials ongoing. Summary Children generally fare well with acute COVID-19 infection, though critical illness is possible. Future research should focus on clarifying the role of children in SARS-CoV-2 transmission and optimal prevention strategies, particularly in the school setting, as well as evaluating pediatric vaccine candidates.

Purpose of review Staphylococcus aureus is the most common invasive bacterial pathogen infecting children in the U.S. and many parts of the world. This major human pathogen continues to evolve, and recognition of recent trends in epidemiology, therapeutics and future horizons is of high importance. Recent findings Over the past decade, a relative rise of methicillin-susceptible S. aureus (MSSA) has occurred, such that methicillin-resistant S. aureus (MRSA) no longer dominates the landscape of invasive disease. Antimicrobial resistance continues to develop, however, and novel therapeutics or preventive modalities are urgently needed. Unfortunately, several recent vaccine attempts proved unsuccessful in humans. Summary Recent scientific breakthroughs highlight the opportunity for novel interventions against S. aureus by interfering with virulence rather than by traditional antimicrobial mechanisms. A S. aureus vaccine remains elusive; the reasons for this are multifactorial, and lessons learned from prior unsuccessful attempts may create a path toward an effective preventive. Finally, new diagnostic modalities have the potential to greatly enhance clinical care for invasive S. aureus disease in children.

Purpose of review We reviewed the literature about parental vaccine hesitancy, focusing on publications from October 2019 to April 2021 to describe patterns and causes of hesitancy and interventions to address hesitancy. Recent findings Recent studies expand understanding of the prevalence of vaccine hesitancy globally and highlight associated individual and contextual factors. Common concerns underlying hesitancy include uncertainty about the need for vaccination and questions about vaccine safety and efficacy. Sociodemographic factors associated with parental vaccine hesitancy vary across locations and contexts. Studies about psychology of hesitancy and how parents respond to interventions highlight the role of cognitive biases, personal values, and vaccination as a social contract or norm. Evidence-based strategies to address vaccine hesitancy include presumptive or announcement approaches to vaccine recommendations, motivational interviewing, and use of immunization delivery strategies like standing orders and reminder/recall programs. A smaller number of studies support use of social media and digital applications to improve vaccination intent. Strengthening school vaccine mandates can improve vaccination rates, but policy decisions must consider local context. Summary Vaccine hesitancy remains a challenge for child health. Future work must include more interventional studies to address hesitancy and regular global surveillance of parental vaccine hesitancy and vaccine content on social media.

Purpose of review The US Centers for Disease Control and Prevention (CDC) classified Clostridioides difficile as an ‘urgent’ public health threat that requires ‘urgent and aggressive action’. This call to action has led to new discoveries that have advanced C. difficile infection (CDI) epidemiology, diagnosis and treatment, albeit predominantly in adults. In 2017, the Infectious Diseases Society of America and Society for Healthcare Epidemiology of America published clinical practice guidelines for both adults and children. At that time, recommendations in children were generally limited to relatively low-quality evidence. Recent findings Since publication of this guidance, there have been many advancements in the understanding of CDI in children. These include better understanding of healthcare settings as uncommon sources of C. difficile acquisition in children; risk factors for recurrent and community-associated CDI; performance of diagnostic tests in children and strategies for optimizing their use; and a more rigorous evidence base for CDI treatment in children, including the first-ever randomized controlled trial of CDI treatment in children and the largest study of fecal microbiota transplantation in children. Summary This review highlights the most recent salient advancements in paediatric CDI knowledge and practice that supplement published clinical guidance provided prior to these advancements.

Purpose of review Neonatal bloodstream infections (BSI) are a major contributor to morbidity and mortality within neonatal intensive care units. BSI, including central line-associated BSI, have decreased over the past 15 years but remain common in extremely preterm infants. The purpose of this review is to highlight recent advances in the causes, diagnosis, management, and prevention of neonatal BSI. Recent findings Continued quality improvement efforts and bundles have reduced BSI incidence, and novel approaches are highlighted. An update of emerging pathogens as well as traditional pathogens with novel antimicrobial resistance, which are an increasingly common cause of neonatal BSI, is included. Finally, current and future investigations into serum or noninvasive biomarkers for neonatal BSI are reviewed. Summary Neonatal BSIs continue to decrease due to enhanced infection control and prevention techniques. However, many challenges remain, including emerging bacterial and fungal resistance and the continued need for novel diagnostics that hasten time to pathogen identification and effective treatment. This review of the past 18 months highlights the rapid changes in this area. Ongoing efforts to reduce the morbidity and mortality caused by neonatal BSI must remain a priority.

Purpose of review Lack of recognition of congenital Chagas disease in infants of mothers from endemic regions who are living in countries nonendemic for Trypanosoma cruzi infection suggests a high rate of underdiagnosis. Pregnancy is the optimal access point for identifying Chagas disease in at-risk mothers and their infants. In this review, we update progress toward implementation of pregnancy-based screening for congenital Chagas disease in nonendemic settings. Recent findings International organizations have updated recommendations for diagnosis, treatment and prevention of congenital Chagas disease. Reports of successful implementation of pregnancy-based screening at some centers provide a model for optimizing diagnosis of congenital Chagas disease. Screening family members of index patients may identify additional T. cruzi-infected persons. Promising tests to augment current diagnostic modalities for maternal and congenital Chagas disease are in development. Universal or risk-based screening would be cost-effective. More healthcare providers are now aware that treatment of congenital Chagas disease is curative and are promoting efforts to make pregnancy-based screening for congenital Chagas disease a standard of care. Summary Ongoing efforts to implement routine pregnancy-based screening for congenital Chagas disease in nonendemic regions will mutually benefit infants, their mothers and family members and can prevent potentially fatal Chagas cardiomyopathy.

Purpose of review Cytomegalovirus (CMV) is the most common viral cause of congenital infection, occurring in approximately 1–2% of live births worldwide. Given our increasing knowledge of risk, advances in the identification of maternal infection, and the extremely limited options for the treatment of fetal infection, the prevention is a promising direction for research efforts. Recently, there have been several exciting studies assessing different ways of preventing congenital infection in the fetus and one in particular has focused on the use of valaciclovir. Recent findings A recent study reported a 71% reduction in vertical transmission of CMV with the use of oral valaciclovir following maternal primary CMV infection early in pregnancy. The clinical impact of this study could be enormous and it has particular implications for considerations around maternal serological screening in the first trimester of pregnancy. Further research assessing behaviour modifications during early pregnancy could also provide evidence for an effective primary prevention technique. Summary Prevention of congenital CMV infection, whether primary, secondary or tertiary, is possible, however, there are barriers to its utilisation in a clinical setting. The main limitation is the requirement for early, effective and large-scale serological screening of mothers to detect asymptomatic primary infection.

Purpose of review Analyses of the host transcriptional response to infection has proved to be an alternative diagnostic strategy to standard direct pathogen detection. This review summarizes the value of applying blood and mucosal transcriptome analyses for the diagnosis and management of children with viral and bacterial infections. Recent findings Over the years, studies have validated the concept that RNA transcriptional profiles derived from children with infectious diseases carry a pathogen-specific biosignature that can be qualitatively and quantitively measured. These biosignatures can be translated into a biologically meaningful context to improve patient diagnosis, as seen in children with tuberculosis, rhinovirus infections, febrile infants and children with pneumonia; understand disease pathogenesis (i.e. congenital CMV) and objectively classify patients according to clinical severity (i.e. respiratory syncytial virus). Summary The global assessment of host RNA transcriptional immune responses has improved our understanding of the host-pathogen interactions in the clinical setting. It has shown the potential to be used in clinical situations wherein our current diagnostic tools are inadequate, guiding the diagnosis and classification of children with infectious diseases.

In vivo reflectance confocal microscopy (RCM) is a non-invasive technique that provides real-time images of the skin structures in a grey scale, at a resolution similar to histopathology, in planes parallel to the skin surface to the depth of the superficial dermis (Gonzalez, 2012). Highly reflective skin components such as melanin acts as an endogenous source of contrast and appear bright (white) in RCM images. Chromoblastomycosis is an infectious disease characterized by the occurrence of verrucous plaques on the limbs.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide causing > 177,100,000 coronavirus disease 2019 (COVID-19) cases by June 18, 2021(World Health Organization, 2021). Uganda, like other African countries, has registered fewer COVID-19 cases and deaths per capita than non-African countries (World Health Organization, 2021). The lower numbers of cases and deaths in Africa by comparison with those in Western countries might be partly due to cross-immunity induced by circulating common cold human corona viruses (HCoVs) (Doshi, 2020).

Introduction…

In Chile, the first patient with COVID-19 was diagnosed in March 2020. The disease spread rapidly, causing a first wave of infections that had its peak on epidemiological week 27, corresponding to the week of July 3rd, 2020, mainly affecting the capital, Santiago.

Background…

Introduction…

Carbapenemase-producing Enterobacterales (CPE) have emerged as a worrying nosocomial issue worldwide. Rapid and accurate detection is crucial to limit the spread of these extremely drug resistant pathogens. Culture-based methods to detect CPEs are often time-consuming and take several days (2 to 5 days). Xpert® Carba-R (Cepheid, France), based on real-time PCR, is now widely used at the first day of admission of “high-risk” patients. The most obvious benefit of this test is that it can be performed directly on rectal swab sample or stools leading to available result in less than an hour after sample proceeding by the laboratory.

On 27 May 2020, WHO updated criteria for releasing COVID-19 patients from isolation, exempting the need to perform a laboratory RT-PCR test [WHO, 2020; WHO, 2020], considering that, even if a positive result is obtained after symptoms resolution, patients are unlikely to be infectious and therefore are not able to originate secondary cases [WHO, 2020]. Aligned with this, the recovery of replication-competent virus from re-positive patients has been unsuccessful [Choi B, 2020; Corral-Lugo A, 2020] and no cases of infection among people who had contact with re-positive patients have been reported to date [Dao TL, 2020; ECDC, 2020; ECDC, 2020; Gao Z, 2020; Kang YJ, 2020].

INTRODUCTION:…

Letter to the Editor…

1. Introduction…

Tuberculosis (TB) caused by the pathogenic agent of Mycobacterium tuberculosis (Mtb), remains a major global health threat. There were approximate 10 million new TB cases and 1.40 million deaths in the world in 2018 (World Health Organization, 2019). Moreover, about half a million of new cases were rifampicin-resistant TB, of which 78% had multidrug-resistant (MDR) TB (World Health Organization, 2019). Although the treatment success rate can reach up to 85% after standard 2HRZE/4HR (a 2-month intensive phase of isoniazid (H), rifampin (R), pyrazinamide (Z), and ethambutol (E), followed by a 4-month continuation phase of rifampin and isoniazid) anti-TB treatment, the treatment cycle is too long to obtain excellent compliance conducing to relapse and drug resistance.

INTRODUCTION…

Introduction…

Abstract Background Legionella spp. are ubiquitous freshwater bacteria responsible for rare but potentially severe cases of Legionnaires’ disease (LD). Legionella sainthelensi is a non-pneumophila Legionella species that was first isolated in 1980 from water near Mt. St-Helens (USA). Although rare cases of LD caused by L. sainthelensi have been reported, very little data is available on this pathogen. Case presentation We describe the first documented case of severe bilateral pleuropneumonia caused by L. sainthelensi. The patient was a 35-year-old woman with Sharp’s syndrome treated with long-term hydroxychloroquine and corticosteroids who was hospitalized for an infectious illness in a university hospital in Reunion Island (France). The patient’s clinical presentation was complicated at first (bilateral pneumonia, multiloculated pleural effusion, then bronchopleural fistula) but her clinical condition eventually improved with the reintroduction of macrolides (spiramycin) in intensive care unit. Etiological diagnosis was confirmed by PCR syndromic assay and culture on bronchoalveolar lavage. Conclusions To date, only 14 documented cases of L. sainthelensi infection have been described worldwide. This pathogen is difficult to identify because it is not or poorly detected by urinary antigen and molecular methods (like PCR syndromic assays that primarily target L. pneumophila and that have only recently been deployed in microbiology laboratories). Pneumonia caused by L. sainthelensi is likely underdiagnosed as a result. Clinicians should consider the possibility of non-pneumophila Legionella infection in patients with a compatible clinical presentation when microbiological diagnostic tools targeted L. pneumophila tested negative.

Abstract Background Few studies on pharyngotonsillitis have examined the clinical presentation of different aetiologies where pathogens have been detected using molecular methods. We aimed to assess how well clinical signs and symptoms can predict (1) the presence or absence of a broad range of viruses and bacteria, and (2) reconsultations for a sore throat or a complication. Methods In this descriptive observational prospective study in primary health care 220 patients aged 15–45 with suspected pharyngotonsillitis were sampled from nose, throat and blood and screened for 20 bacteria and viruses using polymerase chain reaction (PCR), culture and serology. Odds ratios (OR) and predictive values with 95% confidence intervals (CI) were used to show association between microbiological findings and clinical signs and symptoms. Patients were followed up after 3 months by reviewing electronic medical records. Results Both cough and coryza were more common in patients with only viruses (67%) than in patients with only bacteria (21%) (p < 0.001), whereas tonsillar coating was more common in patients with only bacteria (53%) than in patients with only viruses (29%) (p = 0.006). Tonsillar coating (adjusted OR 6.0; 95% CI 2.5–14) and a lack of cough (adjusted OR 3.5; 95% CI 1.5–8.0) were significantly associated with Streptococcus pyogenes (group A streptococci; GAS) and with any bacterial finding. A Centor score of 3–4 had a positive predictive value of 49% (95% CI 42–57) for GAS and 66% (95% CI 57–74) for any bacterial findings. The use of rapid antigen detection test for GAS increased the positive predictive value for this group to 93%. Conclusions Signs and symptoms, both single and combined, were insufficient to rule in GAS or other pathogens. However, both cough and coryza were useful to rule out GAS. The results support the clinical approach of restricting rapid antigen detection testing to patients with 3–4 Centor criteria. The low carriage rate of bacteria among asymptomatic controls implied that most detections in patients represented a true infection.

Abstract Background The ongoing COVID-19 pandemic remains a major challenge for worldwide health care systems and in particular emergency medicine. An early and safe triage in the emergency department (ED) is especially crucial for proper therapy. Clinical symptoms of COVID-19 comprise those of many common diseases; thus, differential diagnosis remains challenging. Method We performed a retrospective study of 314 ED patients presenting with conceivable COVID-19 symptoms during the first wave in Germany. All were tested for COVID-19 with SARS-Cov-2-nasopharyngeal swabs. Forty-seven patients were positive. We analyzed the 267 COVID-19 negative patients for their main diagnosis and compared COVID-19 patients with COVID-19 negative respiratory infections for differences in laboratory parameters, symptoms, and vital signs. Results Among the 267 COVID-19 negative patients, 42.7% had respiratory, 14.2% had other infectious, and 11.2% had cardiovascular diseases. Further, 9.0% and 6.7% had oncological and gastroenterological diagnoses, respectively. Compared to COVID-19 negative airway infections, COVID-19 patients showed less dyspnea (OR 0.440; p = 0.024) but more dysgeusia (OR 7.631; p = 0.005). Their hospital stay was significantly longer (9.0 vs. 5.6 days; p = 0.014), and their mortality significantly higher (OR 3.979; p = 0.014). Conclusion For many common ED diagnoses, COVID-19 should be considered a differential diagnosis. COVID-19 cannot be distinguished from COVID-19 negative respiratory infections by clinical signs, symptoms, or laboratory results. When hospitalization is necessary, the clinical course of COVID-19 airway infections seems to be more severe compared to other respiratory infections. Trial registration: German Clinical Trial Registry DRKS, DRKS-ID of the study: DRKS00021675 date of registration: May 8th, 2020, retrospectively registered.

Abstract Background SARS-CoV-2 poses a considerable threat to those living in residential aged care facilities (RACF). RACF COVID-19 outbreaks have been characterised by the rapid spread of infection and high rates of severe disease and associated mortality. Despite a growing body of evidence supporting airborne transmission of SARS-CoV-2, current infection control measures in RACF including hand hygiene, social distancing, and sterilisation of surfaces, focus on contact and droplet transmission. Germicidal ultraviolet (GUV) light has been used widely to prevent airborne pathogen transmission. Our aim is to investigate the efficacy of GUV technology in reducing the risk of SARS-CoV-2 infection in RACF. Methods A multicentre, two-arm double-crossover, randomised controlled trial will be conducted to determine the efficacy of GUV devices to reduce respiratory viral transmission in RACF, as an adjunct to existing infection control measures. The study will be conducted in partnership with three aged care providers in metropolitan and regional South Australia. RACF will be separated into paired within-site zones, then randomised to intervention order (GUV or control). The initial 6-week period will be followed by a 2-week washout before crossover to the second 6-week period. After accounting for estimated within-zone and within-facility correlations of infection, and baseline infection rates (10 per 100 person-days), a sample size of n = 8 zones (n = 40 residents/zone) will provide 89% power to detect a 50% reduction in symptomatic infection rate. The primary outcome will be the incidence rate ratio of combined symptomatic respiratory infections for intervention versus control. Secondary outcomes include incidence rates of hospitalisation for complications associated with respiratory infection; respiratory virus detection in facility air and fomite samples; rates of laboratory confirmed respiratory illnesses and genomic characteristics. Discussion Measures that can be deployed rapidly into RACF, that avoid the requirement for changes in resident and staff behaviour, and that are effective in reducing the risk of airborne SARS-CoV-2 transmission, would provide considerable benefit in safeguarding a highly vulnerable population. In addition, such measures might substantially reduce rates of other respiratory viruses, which contribute considerably to resident morbidity and mortality. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12621000567820 (registered on 14th May, 2021).

Abstract Background Coccidioidomycosis is a systemic infection caused by dimorphic fungi Coccidioides spp. endemic to Southwestern United States and Central and South America. A history of residence and travel in these areas is essential for the diagnostic of coccidioidomycosis, which has highly variable symptoms ranging from asymptomatic to severe, disseminated infection, and even death. Immunocompromised patients of coccidioidomycosis experience a high risk of dissemination, chronic infection, and mortality. Meningitis is one of the most deleterious coccidioidomycosis and can cause various life-threatening complications. Case presentation Here we report a case of Coccidioides posadasii meningitis in a 49-year-old female who returned to China after one and a half years residence in Los Angeles, USA. The repeated routine cultures using CSF for bacteria or fungi were all negative. To hunt for an infectious etiology, the state-of-the-art technology metagenomic next-generation sequencing (mNGS) was then utilized, suggesting Coccidioides posadasii. Organizational pathological examination and polymerase-chain-reaction (PCR) results subsequently confirmed the mNGS detection. Conclusion To our knowledge, cases for coccidioidal meningitis have been rarely reported in China. While global travelling may spread this disease across continents and make the diagnosis more difficult. mNGS can detect almost all known pathogens with high sensitivity and specificity, especially for uncommon pathogen, such as Coccidioides posadasii in China.

Abstract Background Drug-resistant tuberculosis (DR-TB) remains a major public health concern worldwide. Bedaquiline, a novel diarylquinoline, was added to the WHO-recommended all-oral regimen for patients with multidrug-resistant tuberculosis. We performed a systematic review and meta-analysis to determine the effect of bedaquiline on tuberculosis treatment outcomes. Methods We searched the PubMed, Web of Science and EMBASE databases for relevant studies published up to March 12, 2021. We included studies in which some participants received bedaquiline and others did not. Stata version 16.0 (Stata Corp., College Station, Texas, USA) was used to analyze the results of the meta-analysis. Risk ratios (RRs) with 95% confidence intervals (95% CIs) were calculated to evaluate the effect of bedaquiline on drug-resistant tuberculosis. Between-study heterogeneity was examined by the I-squared test. Randomized controlled trials were assessed for quality using the Jadad scale, and cohort studies were assessed using the Newcastle–Ottawa scale. Results Eight studies, including 2 randomized controlled trials and 6 cohort studies involving a total of 21,836 subjects, were included. When compared with the control, bedaquiline treatment was associated with higher rates of culture conversion (risk ratio (RR):1.272 (1.165–1.389), P < 0.001). We found substantial evidence of a significant reduction in all-cause death (RR: 0.529 (0.454–0.616), P < 0.001)) in the bedaquiline treatment group. There was no significant reduction in treatment success (RR = 0.980 (0.948–1.013, P = 0.234)). Conclusions This study demonstrated that compared with patients who do not receive bedaquiline, this drug has the potential to achieve a higher culture conversion rate and a lower mortality risk among drug-resistant tuberculosis cases.

Abstract Background Ventilator associated pneumonia (VAP) caused by more than one microorganisms is not uncommon and may be potentially challenging, but the relevant data is scarce in ventilated neonates. We aimed to investigate the clinical characteristics and outcomes of polymicrobial VAP in the neonatal intensive care unit (NICU). Methods All neonates with definite diagnosis of VAP from a tertiary level neonatal intensive care unit (NICU) in Taiwan between October 2017 and September 2020 were prospectively observed and enrolled for analyses. All clinical features, therapeutic interventions and outcomes were compared between the polymicrobial VAP and monomicrobial VAP episodes. Multivariate regression analyses were used to find the independent risk factors for treatment failure. Results Among 236 episodes of neonatal VAP, 60 (25.4%) were caused by more than one microorganisms. Polymicrobial VAP episodes were more likely to be associated with multidrug-resistant pathogens (53.3% versus 34.7%, P = 0.014), more often occurred in later days of life and in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. Otherwise most clinical characteristics of polymicrobial VAP were similar to those of monomicrobial VAP. The therapeutic responses and treatment outcomes were also comparable between these two groups, although modification of therapeutic antibiotics were significantly more common in polymicrobial VAP episodes than monomicrobial VAP episodes (63.3% versus 46.2%; P < 0.001). None of any specific pathogens was significantly associated with worse outcomes. Instead, it is the severity of illness, including presence of concurrent bacteremia, septic shock, and requirement of high-frequency oscillatory ventilator and underlying neurological sequelae that are independently associated with treatment failure. Conclusions Polymicrobial VAP accounted for 25.4% of all neonatal VAP in the NICU, and frequently occurred in neonates with prolonged intubation and underlying bronchopulmonary dysplasia. In our cohort, most clinical features, therapeutic responses and final outcomes of neonates with monomicrobial and polymicrobial VAP did not differ significantly.

Misclassification of a phenotype may have direct clinical consequences. Classifying an organism as susceptible to an antibiotic when it is in fact resistant to that antibiotic can result in treatment of individuals with an ineffective agent and may impact the interpretation of clinical trial results.

To investigate the immune systems’ response (and its influencing factors) to vaccination with BNT162b2 or mRNA-1273.

The order Carnivora includes over 300 species that vary many orders of magnitude in size and inhabit all major biomes, from tropical rainforests to polar seas. The high diversity of carnivore parasites represents a source of potential emerging diseases of humans. Zoonotic risk from this group may be driven in part by exceptionally high functional diversity of host species in behavioral, physiological, and ecological traits. We review global macroecological patterns of zoonotic parasites within carnivores, and explore the traits of species that serve as hosts of zoonotic parasites.

by Riho Tateyama-Makino, Mari Abe-Yutori, Taku Iwamoto, Kota Tsutsumi, Motonori Tsuji, Satoru Morishita, Kei Kurita, Yukio Yamamoto, Eiji Nishinaga, Keiichi Tsukinoki SARS-CoV-2 enters host cells when the viral spike protein is cleaved by transmembrane protease serine 2 (TMPRSS2) after binding to the host angiotensin-converting enzyme 2 (ACE2). Since ACE2 and TMPRSS2 are expressed in the tongue and gingival mucosa, the oral cavity is a potential entry point for SARS-CoV-2. This study evaluated the inhibitory effects of general ingredients of toothpastes and mouthwashes on the spike protein-ACE2 interaction and the TMPRSS2 protease activity using an in vitro assay. Both assays detected inhibitory effects of sodium tetradecene sulfonate, sodium N-lauroyl-N-methyltaurate, sodium N-lauroylsarcosinate, sodium dodecyl sulfate, and copper gluconate. Molecular docking simulations suggested that these ingredients could bind to inhibitor-binding site of ACE2. Furthermore, tranexamic acid exerted inhibitory effects on TMPRSS2 protease activity. Our findings suggest that these toothpaste and mouthwash ingredients could help prevent SARS-CoV-2 infection.

by Benjamin Tolchin, Carol Oladele, Deron Galusha, Nitu Kashyap, Mary Showstark, Jennifer Bonito, Michelle C. Salazar, Jennifer L. Herbst, Steve Martino, Nancy Kim, Katherine A. Nash, Max Jordan Nguemeni Tiako, Shireen Roy, Rebeca Vergara Greeno, Karen Jubanyik Background Sequential Organ Failure Assessment (SOFA) score predicts probability of in-hospital mortality. Many crisis standards of care suggest the use of SOFA scores to allocate medical resources during the COVID-19 pandemic. Research question Are SOFA scores elevated among Non-Hispanic Black and Hispanic patients hospitalized with COVID-19, compared to Non-Hispanic White patients? Study design and methods Retrospective cohort study conducted in Yale New Haven Health System, including 5 hospitals with total of 2681 beds. Study population drawn from consecutive patients aged ≥18 admitted with COVID-19 from March 29th to August 1st, 2020. Patients excluded from the analysis if not their first admission with COVID-19, if they did not have SOFA score recorded within 24 hours of admission, if race and ethnicity data were not Non-Hispanic Black, Non-Hispanic White, or Hispanic, or if they had other missing data. The primary outcome was SOFA score, with peak score within 24 hours of admission dichotomized as…

by Haocheng Wu, Chen Wu, Qinbao Lu, Zheyuan Ding, Ming Xue, Junfen Lin Background Zhejiang Province is one of the five provinces in China that had the highest incidence of novel coronavirus disease (COVID-19). Zhejiang, ranked fourth highest in COVID-19 incidence, is located in the Yangtze River Delta region of southeast China. This study was undertaken to identify the space-time characteristics of COVID-19 in Zhejiang. Methods Data on COVID-19 cases in Zhejiang Province from January to July 2020 were obtained from this network system. Individual information on cases and deaths was imported, and surveillance information, including demographic characteristics and geographic and temporal distributions, was computed by the system. The Knox test was used to identify possible space-time interactions to test whether cases that are close in distance were also close in time. Network analysis was performed to determine the relationship among the cases in a transmission community and to try to identify the key nodes. Results In total, 1475 COVID-19 cases and 1 fatal case were reported from January to July 2020 in Zhejiang Province, China. Most of the cases occurred before February 15th, which accounted for 90.10%. The imported cases increased and became the main risk in Zhejiang Province after February 2020. The risk areas showed strong heterogeneity according to the Knox test. The areas at short distances within 1 kilometer and at brief periods within 5 days presented relatively high risk. The numbers of subcommunities for the four clusters were 12, 9, 6 and 4. There was obvious heterogeneity in the modularity of subcommunities. The maximum values of the node centrality for the four clusters were 2.9474, 4.3706, 4.1080 and 2.7500. Conclusions COVID-19 was brought under control over a short period in Zhejiang Province. Imported infections from outside of mainland China then became a new challenge. The effects of spatiotemporal interaction exhibited interval heterogeneity. The characteristics of transmission showed short range and short term risks. The importance to the cluster of each case was detected, and the key patients were identified. It is suggested that we should focus on key patients in complex conditions and in situations with limited control resources.

by Les Jones, Abhijeet Bakre, Hemant Naikare, Ravindra Kolhe, Susan Sanchez, Yung-Yi C. Mosley, Ralph A. Tripp The COVID-19 pandemic caused by the SARS-CoV-2 is a serious health threat causing worldwide morbidity and mortality. Real-time reverse transcription PCR (RT-qPCR) is currently the standard for SARS-CoV-2 detection. Although various nucleic acid-based assays have been developed to aid the detection of SARS-CoV-2 from COVID-19 patient samples, the objective of this study was to develop a diagnostic test that can be completed in 30 minutes without having to isolate RNA from the samples. Here, we present an RNA amplification detection method performed using reverse transcription loop-mediated isothermal amplification (RT-LAMP) reactions to achieve specific, rapid (30 min), and sensitive (…

by Solomon A. Narh-Bana, Mary Kawonga, Esnat D. Chirwa, Latifat Ibisomi, Frank Bonsu, Tobias F. Chirwa Introduction Tuberculosis screening of people living with human immunodeficiency virus is an intervention recommended by the WHO to control the dual epidemic of TB and HIV. The extent to which the intervention is adhered to by the HIV healthcare providers (fidelity) determines the intervention’s effectiveness as measured by patient outcomes, but literature on fidelity is scarce. This study assessed provider implementation fidelity to national guidelines on TB screening at HIV clinics in Ghana. Methods It was a cross-sectional study that used structured questionnaires to gather data, involving 226 of 243 HIV healthcare providers in 27 HIV clinics across Ghana. The overall fidelity score comprised sixteen items with a maximum score of 48 grouped into three components of the screening intervention (TB diagnosis, TB awareness and TB symptoms questionnaire). Simple summation of item scores was done to determine fidelity score per provider. In this paper, we define the level of fidelity as low if the scores were below the median score and were otherwise categorized as high. Background factors potentially associated with implementation fidelity level were assessed using cluster-based logistic regression. Odds ratio with 95% confidence interval (CI) was used as the measure of association. Results Of the 226 healthcare providers interviewed, 60% (135) were females with a mean age of 34.5 years (SD = 8.3). Most of them were clinicians [63% (142)] and had post-secondary non-tertiary education [62% (141)]. Overall, 53% (119) of the healthcare providers were categorized to have implemented the intervention with high fidelity. Also, 56% (126), 53% (120), and 59% (134) of the providers implemented the TB diagnosis, TB awareness and TB symptoms questionnaire components respectively with high fidelity. After adjusting for cluster effect, female providers (AOR = 2.36, 95%CI: 1.09–5.10, p =…

by Benjamin Demah Nuertey, Kwame Ekremet, Abdul-Rashid Haidallah, Kareem Mumuni, Joyce Addai, Rosemary Ivy E. Attibu, Michael C. Damah, Elvis Duorinaa, Anwar Sadat Seidu, Victor C. Adongo, Richard Kujo Adatsi, Hisyovi Caedenas Suri, Abass Abdul-Karim Komei, Braimah Baba Abubakari, Enoch Weyori, Emmanuel Allegye-Cudjoe, Augustina Sylverken, Michael Owusu, Richard O. Phillips Introduction Coronavirus disease-19 (COVID-19), which started in late December, 2019, has spread to affect 216 countries and territories around the world. Globally, the number of cases of SARS-CoV-2 infection has been growing exponentially. There is pressure on countries to flatten the curves and break transmission. Most countries are practicing partial or total lockdown, vaccination, massive education on hygiene, social distancing, isolation of cases, quarantine of exposed and various screening approaches such as temperature and symptom-based screening to break the transmission. Some studies outside Africa have found the screening for fever using non-contact thermometers to lack good sensitivity for detecting SARS-CoV-2 infection. The aim of this study was to determine the usefulness of clinical symptoms in accurately predicting a final diagnosis of COVID-19 disease in the Ghanaian setting. Method The study analysed screening and test data of COVID-19 suspected, probable and contacts for the months of March to August 2020. A total of 1,986 participants presenting to Tamale Teaching hospital were included in the study. Logistic regression and receiver operator characteristics (ROC) analysis were carried out. Results Overall SARS-CoV-2 positivity rate was 16.8%. Those with symptoms had significantly higher positivity rate (21.6%) compared with asymptomatic (17.0%) [chi-squared 15.5, p-value,…

by Rhiannon Edge, Josh Meyers, Gabriella Tiernan, Zhicheng Li, Alexandra Schiavuzzi, Priscilla Chan, Amy Vassallo, April Morrow, Carolyn Mazariego, Claire E. Wakefield, Karen Canfell, Natalie Taylor The COVID-19 pandemic has dramatically impacted cancer care worldwide. Disruptions have been seen across all facets of care. While the long-term impact of COVID-19 remains unclear, the immediate impacts on patients, their carers and the healthcare workforce are increasingly evident. This study describes disruptions and reorganisation of cancer services in Australia since the onset of COVID-19, from the perspectives of people affected by cancer and healthcare workers. Two separate online cross-sectional surveys were completed by: a) cancer patients, survivors, carers, family members or friends (n = 852) and b) healthcare workers (n = 150). Descriptive analyses of quantitative survey data were conducted, followed by inductive thematic content analyses of qualitative survey responses relating to cancer care disruption and perceptions of telehealth. Overall, 42% of cancer patients and survivors reported experiencing some level of care disruption. A further 43% of healthcare workers reported atypical delays in delivering cancer care, and 50% agreed that patient access to research and clinical trials had been reduced. Almost three quarters (73%) of patients and carers reported using telehealth following the onset of COVID-19, with high overall satisfaction. However, gaps were identified in provision of psychological support and 20% of participants reported that they were unlikely to use telehealth again. The reorganisation of cancer care increased the psychological and practical burden on carers, with hospital visitation restrictions and appointment changes reducing their ability to provide essential support. COVID-19 has exacerbated a stressful and uncertain time for people affected by cancer and healthcare workers. Service reconfiguration and the adoption of telehealth have been essential adaptations for the pandemic response, offering long-term value. However, our findings highlight the need to better integrate psychosocial support and the important role of carers into evolving pandemic response measures. Learnings from this study could inform service improvements that would benefit patients and carers longer-term.

by Marcello Barbosa Otoni Gonçalves Guedes, Sanderson José Costa de Assis, Geronimo José Bouzas Sanchis, Diego Neves Araujo, Angelo Giuseppe Roncalli Da Costa Oliveira, Johnnatas Mikael Lopes Background Brazil, as many other countries, have been heavily affected by COVID-19. This study aimed to analyze the impact of Primary health care and the family health strategy (FHS) coverage, the scores of the National Program for Improving Primary Care Access and Quality (PMAQ), and socioeconomic and social indicators in the number of COVID-19 cases in Brazilian largest cities. Methods This is an ecological study, carried out through the analysis of secondary data on the population of all Brazilian main cities, based on the analysis of a 26-week epidemiological epidemic week series by COVID-19. Statistical analysis was performed using Generalized Linear Models with an Autoregressive work correlation matrix. Results It was shown that greater PHC coverage and greater FHS coverage together with an above average PMAQ score are associated with slower dissemination and lower burden of COVID-19. Conclusion It is evident that cities with less social inequality and restrictions of social protection combined with social development have a milder pandemic scenario. It is necessary to act quickly on these conditions for COVID-19 dissemination by timely actions with high capillarity. Expanding access to PHC and social support strategies for the vulnerable are essential.

by Theophilus Quaye, Patrick Williams Narkwa, Seth A. Domfeh, Gloria Kattah, Mohamed Mutocheluh Hepatitis B vaccination is the most effective preventive measure in reducing the incidence of chronic hepatitis B virus (HBV) infection and its consequences such as cirrhosis, hepatocellular carcinoma, liver failure and death. Ghana introduced the universal HBV vaccination in the national Expanded Programme on Immunization in 2002. The current study sought to determine the sero-protection rate and the prevalence of HBV infection among fully vaccinated children in the West Gonja District in the Savanna Region of Ghana. This cross-sectional study recruited three hundred and fifty (350) fully vaccinated children who visited West Gonja Catholic Hospital from September to December 2019 for healthcare. Structured questionnaires were administered to obtain information on the demographics. The clinical history of the participants was obtained from the hospital records. Sera were separated from 2-5ml of blood sample collected from each participant after informed consent had been sought from their parents/guardians. Sera were tested for HBsAg, anti-HBs and anti-HBc using ELISA. Samples positive for HBsAg or anti-HBc were tested for HBV DNA by Real-Time Polymerase Chain Reaction. The overall sero-protection rate (anti-HBs titers ≥ 10 mIU/mL) among the studied participants was 56% with anti-HBs geometric mean titer (GMT) of 95.7 mIU/mL (± 6.0; 95% CI) compared with GMT of 2.8 mIU/mL (± 0.2; 95% CI) among non-seroprotected participants. There was no statistically significant difference in sero-protection rate between males and females (p-value = 0.93) and in relation to age (p-value = 0.20). The prevalence of HBV infection among studied participants as determined by the HBV DNA/HBsAg positivity was 1.4% while anti-HBc sero-positivity was 2%. Even though the sero-protection rate and HBV infection rate reported in the current study compares with that of other international studies further studies need to be conducted to understand the factors related to sero-protection and HBV infection rate in the Savanna Region of Ghana.

by Gregg Hartvigsen There remains a great challenge to minimize the spread of epidemics, especially in high-density communities such as colleges and universities. This is particularly true on densely populated, residential college campuses. To construct class and residential networks data from a four-year, residential liberal arts college with 5539 students were obtained from SUNY College at Geneseo, a rural, residential, undergraduate institution in western NY, USA. Equal-sized random networks also were created for each day. Different levels of compliance with mask use (none to 100%), mask efficacy (50% to 100%), and testing frequency (daily, or every 2, 3, 7, 14, 28, or 105 days) were assessed. Tests were assumed to be only 90% accurate and positive results were used to isolate individuals. The effectiveness of contact tracing, and the effect of quarantining neighbors of infectious individuals, was tested. The structure of the college course enrollment and residence networks greatly influenced the dynamics of the epidemics, as compared to the random networks. In particular, average path lengths were longer in the college networks compared to random networks. Students in larger majors generally had shorter average path lengths than students in smaller majors. Average transitivity (clustering) was lower on days when students most frequently were in class (MWF). Degree distributions were generally large and right skewed, ranging from 0 to 719. Simulations began by inoculating twenty students (10 exposed and 10 infectious) with SARS-CoV-2 on the first day of the fall semester and ended once the disease was cleared. Transmission probability was calculated based on an R0 = 2.4. Without interventions epidemics resulted in most students becoming infected and lasted into the second semester. On average students in the college networks experienced fewer infections, shorter duration, and lower epidemic peaks when compared to the dynamics on equal-sized random networks. The most important factors in reducing case numbers were the proportion masking and the frequency of testing, followed by contact tracing and mask efficacy. The paper discusses further high-order interactions and other implications of non-pharmaceutical interventions for disease transmission on a residential college campus.

by Saman Hewamana, Thurairajah Skandarajah, Chathuri Jayasinghe, Samadhi Deshapriya, Dhananjani Senarathna, Gehan Arseculeratne, Mahesh Harischandra, Gnani Somasundaram, Vadivelu Srinivasan, Surjit Somiah, Nihal Munasinghe, Sangeetha Hewawasam, Lalith Ekanayake, Rohini Wadanamby, Geethani Galagoda, Thet Thet Lin, Jayantha Balawardena Background The Covid-19 pandemic has caused significant morbidity and mortality among patients with cancer. Most countries employed measures to prevent spread of Covid-19 infection which include shielding, quarantine, lockdown, travel restrictions, physical distancing and the use of personal protective equipment. This study was carried out to assess the change in patient attendance and the efficacy of newly implemented strategies to mitigate the impact of Covid-19 on services at the Lanka Hospital Blood Cancer Centre (LHBCC) in Colombo, Sri Lanka. Methodology Telephone consultation, infection control, personal protective measures and emergency admission policy were implemented with the aim of having a Covid-19 free ward and to prevent cross-infections. This descriptive cross-sectional study was conducted with 1399 patient episodes (in-patient care or day-case review). We analysed patients treated as in-patient as well as day-case basis between 01st April 2020 and 31st December 2020. Results There were 977 day-case based episodes and 422 in-patient based episodes. There was a 14% drop in episode numbers compared to same period in 2019. There was no cross infection and no patients with Covid-19 related symptoms or positive test results entered the LHBCC during the study period. Conclusion Services in blood cancer care were maintained to prevent late stage presentation and adverse outcome. Measures implemented to prevent Covid-19 were effective to allow continuation of treatment. This study highlights the importance of implementing strict protocols, clinical screening, use of appropriate personal protective equipment in delivering blood cancer care during the Covid-19 pandemic. This is the only documented study relating to outcome and successful applicability of measures to prevent spread of Covid-19 infection and maintaining services among blood cancer patients in Sri Lanka.