Rickettsiosis with Pleural Effusion: A Systematic Review with a Focus on Rickettsiosis in Italy

Background: Motivated by a case finding of Mediterranean spotted fever (MSF) associated with atypical pneumonia and pleural effusion in which Rickettsia conorii subsp. israelensis was identified by molecular methods in the pleural fluid, we wanted to summarize the clinical presentations of rickettsiosis in Italy by systematic research and to make a systematic review of all the global cases of rickettsiosis associated with pleural effusion. Methods: For the literature search, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. We chose to select only the studies published in last 25 years and confirmed both with serological and molecular assays. Results: Human cases of rickettsiosis in Italy were reported in 48 papers describing 2831 patients with very different clinical presentations; the majority was MSF accounted to R. conorii and was reported in Sicily. Pleural effusion associated with infection with microorganisms belonging to Rickettsiales was described in 487 patients. It was rarely associated with microorganisms different from O. tsutsugamushi; also rarely, cases of scrub typhus were reported outside Southeast Asia and in the largest majority, the diagnosis was achieved with serology. Conclusions: MSF, especially when caused by R. conorii subsp. israelensis, may be a severe disease. A high index of suspicion is required to promptly start life-saving therapy. Pleural effusion and interstitial pneumonia may be part of the clinical picture of severe rickettsial disease and should not lead the physician away from this diagnosis

Vaccines for Mycoplasma Diseases of Small Ruminants: A Neglected Area of Research

Mycoplasmas cause some of the most economically important diseases of sheep and goats, including diseases listed by the World Organisation for Animal Health (OIE) such as contagious caprine pleuropneumonia (CCPP) and contagious agalactia (CA). Other important mycoplasma diseases include chronic respiratory and arthritic syndrome (CRAS) and atypical pneumonia, both present on all continents where small ruminants are farmed. Unfortunately, owing to a lack of investment, most commercial vaccines for these diseases are of poor quality, being mostly composed of killed bacteriocins of dubious or unknown efficacy. Several Mediterranean laboratories produce autogenous vaccines, but these can only be used on farms where outbreaks have been officially declared, and consequently have limited impact on disease nationally. Effective live vaccines are available, but their use is often restricted because of safety concerns. With the necessary safeguards in place, we argue for their greater use. This review examines reported vaccines for mycoplasma diseases of small ruminants and attempts to identify new candidate antigens that may enable the development of improved products. Vaccines for CCPP are covered elsewhere.

Coronavirus - Drug Discovery and Therapeutic Drug Monitoring Options

COVID-19 is basically a medium size RNA virus and the nucleic acid is about 30 kb long, positive in sense, single stranded and polyadenylated. The RNA which is found in this virus is the largest known RNA and codes for a large polyprotein. In addition, coronaviruses are capable of genetic recombination if 2 viruses infect the same cell at the same time. SARS-CoV emerged first in southern China and rapidly spread around the globe in 2002–2003. In November 2002, an unusual epidemic of atypical pneumonia with a high rate of nosocomial transmission to health-care workers occurred in Foshan, Guangdong, China. In March 2003, a novel CoV was confirmed to be the causative agent for SARS, and was thus named SARS-CoV. Despite the report of a large number of virus-based and host-based treatment options with potent in vitro activities for SARS and MERS, only a few are likely to fulfil their potential in the clinical setting in the foreseeable future. Most drugs have one or more major limitations that prevent them from proceeding beyond the in vitro stage. First, many drugs have high EC50/Cmax ratios at clinically relevant dosages

Histological Changes in the Kidneys and Heart in Experimental Acanthamoebiasis in Immunocompetent and Immunosuppressed Hosts

The course of Acanthamoeba spp. infection depends on the age and immune status of the host, and the virulence of the Acanthamoeba spp. strain. Some strains of free-living amoebae exhibit organ specificity, during the course of infection, while others may cause changes in many organs or completely lose pathogenicity. The aim of the current study was to investigate the pathological properties of Acanthamoeba spp. isolated from a patient with acute myeloid leukemia and atypical pneumonia (AM22). Moreover, the objective was to investigate the histopathological changes in the kidneys and heart of immunocompetent and immunosuppressed mice infected with Acanthamoeba spp. Amoebae were re-isolated from both the kidneys and hearts of the inoculated mice, although no cysts or trophozoites of the amoebae were detected in microscopic slides of the fragments of these organs. Acanthamoeba spp. induced changes in the kidney and heart weight of infected mice. In immunocompetent and immunosuppressed Acanthamoeba spp. infected mice, we found some histopathological changes, including areas with less acidic cytoplasm and a relaxation of muscle fibers. In further studies, it is important to analyze changes in gene and protein expressions in the heart and kidneys of hosts with disseminated acanthamoebiasis to better understand the course of infection in these organs, because the results of histological analysis varied depending on the immune status and duration of infection.

The Relationships among Anxiety, Subjective Well-Being, Media Consumption, and Safety-Seeking Behaviors during the COVID-19 Epidemic

The COVID-19 epidemic has been confirmed as the largest scale outbreak of atypical pneumonia since the outbreak of severe acute respiratory syndrome (SARS) in 2003 and it has become a public health emergency of international concern. It exacerbated public confusion and anxiety, and the impact of COVID-19 on people needs to be better understood. Indeed, prior studies that conducted meta-analysis of longitudinal cohort research compared mental health before versus during the COVID-19 pandemic and proved that public health polices (e.g., city lockdowns, quarantines, avoiding gatherings, etc.) and COVID-19-related information that circulates on new media platforms directly affected citizen’s mental health and well-being. Hence, this research aims to explore Taiwanese people’s health status, anxiety, media sources for obtaining COVID-19 information, subjective well-being, and safety-seeking behavior during the COVID-19 epidemic and how they are associated. Online surveys were conducted through new media platforms, and 342 responses were included in the analysis. The research results indicate that the participants experienced different aspects of COVID-19 anxiety, including COVID-19 worry and perceived COVID-19 risk. Among the given media sources, the more participants searched for COVID-19 information on new media, the greater they worried about COVID-19. Furthermore, COVID-19 worry was positively related to safety-seeking behavior, while perceived COVID-19 risk was negatively related to subjective well-being. This paper concludes by offering some suggestions for future studies and pointing out limitations of the present study.

Community-Acquired Respiratory Distress Syndrome Toxin: Unique Exotoxin for M. pneumoniae

Mycoplasma pneumoniae infection often causes respiratory diseases in humans, particularly in children and adults with atypical pneumonia and community-acquired pneumonia (CAP), and is often exacerbated by co-infection with other lung diseases, such as asthma, bronchitis, and chronic obstructive pulmonary disorder. Community-acquired respiratory distress syndrome toxin (CARDS TX) is the only exotoxin produced by M. pneumoniae and has been extensively studied for its ADP-ribosyltransferase (ADPRT) activity and cellular vacuolization properties. Additionally, CARDS TX induces inflammatory responses, resulting in cell swelling, nuclear lysis, mucus proliferation, and cell vacuolization. CARDS TX enters host cells by binding to the host receptor and is then reverse transported to the endoplasmic reticulum to exert its pathogenic effects. In this review, we focus on the structural characteristics, functional activity, distribution and receptors, mechanism of cell entry, and inflammatory response of CARDS TX was examined. Overall, the findings of this review provide a theoretical basis for further investigation of the mechanism of M. pneumoniae infection and the development of clinical diagnosis and vaccines.

Coronavirus - Drug Discovery and Therapeutic Options

COVID-19 is basically a medium size RNA virus and the nucleic acid is about 30 kb long, positive in sense, single stranded and polyadenylated. The RNA which is found in this virus is the largest known RNA and codes for a large polyprotein. In addition, coronaviruses are capable of genetic recombination if 2 viruses infect the same cell at the same time. SARS-CoV emerged first in southern China and rapidly spread around the globe in 2002–2003. In November 2002, an unusual epidemic of atypical pneumonia with a high rate of nosocomial transmission to health-care workers occurred in Foshan, Guangdong, China. In March 2003, a novel CoV was confirmed to be the causative agent for SARS, and was thus named SARS-CoV. Despite the report of a large number of virus-based and host-based treatment options with potent in vitro activities for SARS and MERS, only a few are likely to fulfil their potential in the clinical setting in the foreseeable future. Most drugs have one or more major limitations that prevent them from proceeding beyond the in vitro stage. First, many drugs have high EC50/Cmax ratios at clinically relevant dosages.

Identification of potential inhibitors of SARS-CoV-2 S protein–ACE2 interaction by in silico drug repurposing

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a new coronavirus discovered that appeared in Wuhan, China, in December 2019, causes COVID-19 disease which have resulted in cases similar to SARS-atypical pneumonia. Worldwide, around 116 million cases and 2.57 million deaths are reported with new cases and increasing mortality every day. To date, there is no specific commercial treatment to control the infection. Repurpose drugs targeting the angiotensin-converting enzyme 2 (ACE2) receptor represents an alternative strategy to block the binding of SARS-CoV-2 protein S and forestall virus adhesion, internalization, and replication in the host cell. Methods: We performed a rigid molecular docking using the receptor binding domain of the S1 subunit of S protein (RBD S1)-ACE2 (PDB ID: 6VW1) interaction site and 1,283 drugs FDA approved. The docking score, frequency of the drug in receptor site, and interactions at the binding site residues were used as analyzing criteria. Results: This research yielded 40 drugs identified as a potential inhibitor of RBD S1-ACE2 interaction. Among the inhibitors, compounds such as ipratropium, formoterol, and fexofenadine can be found. Specialists employ these drugs as therapies to treat chronic obstructive pulmonary disease, asthma and virtually any respiratory infection. Conclusions: Our results will serve as the basis for in vitro and in vivo studies to evaluate the potential use of those drugs to generate affordable and convenient therapies to treat COVID-19.