Streptococcus pneumoniae and Its Virulence Factors H2O2 and Pneumolysin Are Potent Mediators of the Acute Chest Syndrome in Sickle Cell Disease.

Sickle cell disease (SCD) is one of the most common autosomal recessive disorders in the world. Due to functional asplenia, a dysfunctional antibody response, antibiotic drug resistance and poor response to immunization, SCD patients have impaired immunity. A leading cause of hospitalization and death in SCD patients is the acute chest syndrome (ACS). This complication is especially manifested upon infection of SCD patients with Streptococcus pneumoniae (Spn)-a facultative anaerobic Gram-positive bacterium that causes lower respiratory tract infections. Spn has developed increased rates of antibiotics resistance and is particularly virulent in SCD patients. The primary defense against Spn is the generation of reactive oxygen species (ROS) during the oxidative burst of neutrophils and macrophages. Paradoxically, Spn itself produces high levels of the ROS hydrogen peroxide (H2O2) as a virulence strategy. Apart from H2O2, Spn also secretes another virulence factor, i.e., the pore-forming exotoxin pneumolysin (PLY), a potent mediator of lung injury in patients with pneumonia in general and particularly in those with SCD. PLY is released early on in infection either by autolysis or bacterial lysis following the treatment with antibiotics and has a broad range of biological activities. This review will discuss recent findings on the role of pneumococci in ACS pathogenesis and on strategies to counteract the devastating effects of its virulence factors on the lungs in SCD patients.

Infectious aetiologies of severe acute chest syndrome in sickle-cell adult patients, combining conventional microbiological tests and respiratory multiplex PCR.

Acute chest syndrome (ACS) is the most serious complication of sickle cell disease. The pathophysiology of ACS may involve lower respiratory tract infection (LRTI), alveolar hypoventilation and atelectasis, bone infarcts-driven fat embolism, and in situ pulmonary artery thrombosis. One of the most challenging issues for the physicians is to diagnose LRTI as the cause of ACS. The use of a respiratory multiplex PCR (mPCR) for the diagnosis of LRTI has not been assessed in sickle-cell adult patients with ACS. To describe the spectrum of infectious aetiologies of severe ACS, using a diagnostic approach combining conventional tests and mPCR. A non-interventional monocenter prospective study involving all the consecutive sickle-cell adult patients with ACS admitted to the intensive care unit (ICU). Microbiological investigation included conventional tests and a nasopharyngeal swab for mPCR. Altogether, 36 patients were enrolled, of whom 30 (83%) had complete microbiological investigations. A bacterial microorganism, mostly Staphylococcus aureus (n = 8), was identified in 11 patients. There was no pneumonia-associated intracellular bacterial pathogen. A respiratory virus was identified in six patients. Using both conventional tests and nasopharyngeal mPCR, a microbiological documentation was obtained in half of adult ACS patients admitted to the ICU. Pyogenic bacteria, especially S. aureus, predominated.

Caracterización de la miocarditis por COVID-19 mediante resonancia magnética cardiaca / Cardiac magnetic resonance characterization of COVID-19 myocarditis

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Respiratory pathogens and acute chest syndrome in children with sickle cell disease.

BACKGROUND: Acute chest syndromes (ACS) may be associated with upper respiratory tract infections, but the epidemiology of viral and intracellular respiratory pathogens in children with sickle cell disease (SCD) is not precisely known. The aim of this study was to describe the epidemiology of viral and intracellular respiratory pathogens in children with SCD presenting with fever and/or ACS. MATERIALS AND METHODS: An observational, prospective, single-centre cohort study with nested case-control analysis was conducted on children with SCD admitted from October 2016 to October 2017 for fever and/or ACS to the paediatric department of Robert Debré university hospital, Paris, France. They were screened for 20 respiratory pathogens by a multiplex PCR in the nasopharynx (FilmArray). RESULTS: We included 101 children. M/F sex ratio of 0.45. The median age was 3.2 years (IQR: 1.4-8.2). At least one pathogen was isolated in 67 patients (67%). The most frequent viruses were as follows: rhinovirus (n=33), adenovirus (n=14), respiratory syncytial virus (n=13) and parainfluenza viruses (n=11). Mycoplasma pneumoniae was detected in one case. Twenty-three (23%) presented with or developed ACS. A nested case-control analysis was performed, after pairing ACS with non-ACS children for age and inclusion period. There was no statistical association between any viral detection or multiple viral infection, and ACS (p=0.51) even though parainfluenza viruses were twice as common in ACS. CONCLUSIONS: Viral detection in febrile children with SCD is frequent, but its association with ACS was not demonstrated. In this study, M. pneumoniae was rare in young children with SCD experiencing ACS.

Molecular testing for respiratory pathogens in sickle cell disease adult patients presenting with febrile acute chest syndrome.

BACKGROUND: Differentiating acute chest syndrome (ACS) from community-acquired pneumonia (CAP) is challenging in adults presenting with major sickle cell disease (SCD) (semiological similarity, rare microbiological documentation). We aimed to assess the usefulness of nucleic acid amplification test (NAAT) for respiratory pathogens, in combination with standard bacteriological investigations, in febrile ACS adult patients presenting with major SCD. METHODS: We performed a prospective, monocentric, observational study of 61 SCD adults presenting with febrile ACS from February 2015 to April 2016. Systematic blood, urine, and respiratory specimens were collected, before antibiotic initiation, for culture, urinary antigen tests, serology, and NAAT for respiratory pathogens. RESULTS: A pathogen was detected in 12 febrile ACS (19.7%): four viruses (6.6%) (Rhinovirus; Influenza A/B), seven bacteria (11.4%) (S. aureus, S. pneumoniae, K. pneumoniae, L. pneumophila, M. pneumoniae), one mixed infection (1.6%) (S. aureus and Influenza B). NAAT only detected L. pneumophila in one case (serogroup 2). Apart from a significantly shorter antibiotic therapy duration (6.1 vs. 7.8 days, P=0.045), no difference was observed between undocumented and microbiologically-documented febrile ACS. CONCLUSION: Using NAAT for the detection of respiratory pathogens in adults presenting with SCD slightly improved the microbiological diagnostic of febrile ACS, although respiratory infections are not the main etiological factor.

Antibiotics for treating acute chest syndrome in people with sickle cell disease.

BACKGROUND: The clinical presentation of acute chest syndrome is similar whether due to infectious or non-infectious causes, thus antibiotics are usually prescribed to treat all episodes. Many different pathogens, including bacteria, have been implicated as causative agents of acute chest syndrome. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. This is an update of a Cochrane Review first published in 2007, and most recently updated in 2015. OBJECTIVES: To determine whether an empirical antibiotic treatment approach (used alone or in combination):1. is effective for acute chest syndrome compared to placebo or standard treatment;2. is safe for acute chest syndrome compared to placebo or standard treatment;Further objectives are to determine whether there are important variations in efficacy and safety:3. for different treatment regimens,4. by participant age, or geographical location of the clinical trials. SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 23 October 2017), African Index Medicus (1982 to 23 October 2017) and trial registries (23 October 2017).Date of most recent search of the Haemoglobinopathies Trials Register: 10 July 2019. SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data and assess trial quality by standard Cochrane methodologies, but no eligible randomised controlled trials were identified. MAIN RESULTS: For this update, we were unable to find any randomised controlled trials on antibiotic treatment approaches for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: This update was unable to identify randomised controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. While randomised controlled trials are needed to establish the optimum antibiotic treatment for this condition, we do not envisage further trials of this intervention will be conducted, and hence the review will no longer be regularly updated.

ACS in children with sickle cell anaemia in Uganda: prevalence, presentation and aetiology.

ACS (ACS) is a serious complication of sickle cell anaemia (SCA). We set out to describe the burden, presentation and organisms associated with ACS amongst children with SCA attending Mulago Hospital, Kampala, Uganda. In a cross-sectional study, 256 children with SCA and fever attending Mulago Hospital were recruited. Chest X-rays, blood cultures, complete blood count and sputum induction were performed. Sputum samples were investigated by Ziehl-Nielsen staining, culture and DNA polymerase chain reaction (PCR) for Chlamydia pneumoniae. Of the 256 children, 22·7% had ACS. Clinical and laboratory findings were not significantly different between children with ACS and those without, besides cough and abnormal signs on auscultation. Among the 83 sputum cultures Streptococcus pneumoniae (12%) and Moraxella spp (8%), were the commonest. Of the 59 sputa examined with DNA PCR, 59·3% were positive for Chlamydia pneumoniae. Mycobacterium tuberculosis was isolated in 6/83 sputa. These results show that one in 5 SCA febrile children had ACS. There were no clinical and laboratory characteristics of ACS, but cough and abnormalities on auscultation were associated with ACS. The high prevalence of Chlamydia pneumoniae in children with ACS in this setting warrants the addition of macrolides to treatment, and M. tuberculosis should be differential in sub-Saharan children with ACS.

Antibiotics for treating acute chest syndrome in people with sickle cell disease.

BACKGROUND: The clinical presentation of acute chest syndrome is similar whether due to infectious or non-infectious causes, thus antibiotics are usually prescribed to treat all episodes. Many different pathogens, including bacteria, have been implicated as causative agents of acute chest syndrome. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. This is an update of a Cochrane review first published in 2007, and previously updated in 2013. OBJECTIVES: To determine whether an empirical antibiotic treatment approach (used alone or in combination):1. is effective for acute chest syndrome compared to placebo or standard treatment;2. is safe for acute chest syndrome compared to placebo or standard treatment;Further objectives are to determine whether there are important variations in efficacy and safety:3. for different treatment regimens,4. by participant age, or geographical location of the clinical trials. SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 23 February 2015), African Index Medicus (1982 to 23 February 2015). and the World Health Organization International Clinical Trials Registry Platform Search Portal (23 February 2015).Date of most recent search of the Haemoglobinopathies Trials Register: 20 January 2015. SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data and assess trial quality by standard Cochrane Collaboration methodologies, but no eligible randomised controlled trials were identified. MAIN RESULTS: For this update, we were unable to find any randomised controlled trials on antibiotic treatment approaches for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: This update was unable to identify randomised controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. Randomised controlled trials are needed to establish the optimum antibiotic treatment for this condition.

Antibiotics for treating acute chest syndrome in people with sickle cell disease.

BACKGROUND: The clinical presentation of acute chest syndrome is similar whether due to infectious or non-infectious causes, thus antibiotics are usually prescribed to treat all episodes. Many different pathogens, including bacteria, have been implicated as causative agents of acute chest syndrome. There is no standardized approach to antibiotic therapy and treatment is likely to vary from country to country. Thus, there is a need to identify the efficacy and safety of different antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. OBJECTIVES: To determine whether an empirical antibiotic treatment approach (used alone or in combination): 1. is effective for acute chest syndrome compared to placebo or standard treatment; 2. is safe for acute chest syndrome compared to placebo or standard treatment;Further objectives are to determine whether there are important variations in efficacy and safety: 3. for different treatment regimens, 4. by participant age, or geographical location of the clinical trials. SEARCH METHODS: We searched The Group's Haemoglobinopathies Trials Register, which comprises references identified from comprehensive electronic database searches and handsearching of relevant journals and abstract books of conference proceedings. We also searched the LILACS database (1982 to 19 October 2012), African Index Medicus (1982 to 3 November 2012). and the World Health Organization International Clinical Trials Registry Platform Search Portal (19 October 2012).Date of most recent search of the Haemoglobinopathies Trials Register: 29 October 2012. SELECTION CRITERIA: We searched for published or unpublished randomised controlled trials. DATA COLLECTION AND ANALYSIS: Each author intended to independently extract data and assess trial quality by standard Cochrane Collaboration methodologies, but no eligible randomised controlled trials were identified. MAIN RESULTS: For this update, we were unable to find any randomised controlled trials on antibiotic treatment approaches for acute chest syndrome in people with sickle cell disease. AUTHORS' CONCLUSIONS: This update was unable to identify randomised controlled trials on efficacy and safety of the antibiotic treatment approaches for people with sickle cell disease suffering from acute chest syndrome. Randomised controlled trials are needed to establish the optimum antibiotic treatment for this condition.

[Bordetella bronchiseptica-associated acute chest syndrome in a child with sickle cell disease]. / Syndrome thoracique aigu associé à une infection àBordetella bronchiseptica chez un enfant drépanocytaire.

We describe a case of acute chest syndrome associated with Bordetella bronchiseptica pneumonia in a child with sickle cell disease. B. bronchiseptica is recognized as an important pathogen of the respiratory tract for a large variety of animal species. This zoonotic agent has been frequently associated with chronic and recurrent infections. In humans, the bacterium acts as an opportunistic pathogen affecting mostly immunocompromised patients or those with preexisting respiratory diseases. This case and literature review provides an opportunity to discuss the risk factors, treatment, follow-up, and prevention of such zoonotic infections in the context of a lack of cross-protection of new pertussis vaccines.