Association of myocarditis and acute renal failure complicating meningococcal septicaemia

Dacosta, D.F.; Neville, E.; Raman, Gowri

doi:10.1016/s0163-4453(05)80008-8

Cited by 4 publications

(1 citation statement)

References 2 publications

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“…In industrialized countries heart failure combined with persistent hypotension are the primary causes of death in meningococcal disease. Acute heart failure has previously been attributed to inflammatory foci in the myocardium (Ferguson and Chapman, 1948;Dacosta et al, 1991;Neveling and Kaschula, 1993;Garcia et al, 1999). Troponin I, a specific marker of myocardial impairment and cell death, increased within 48 h of hospital admission of meningococcal shock patients and was related to a clinical severity score (Thiru et al, 2000).…”

Section: Transcriptional Profiles In Heart Tissue Samplesmentioning

confidence: 98%

Extensive Changes in Transcriptomic “Fingerprints” and Immunological Cells in the Large Organs of Patients Dying of Acute Septic Shock and Multiple Organ Failure Caused by Neisseria meningitidis

Brusletto

Løberg

Hellerud

et al. 2020

Front. Cell. Infect. Microbiol.

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Background: Patients developing meningococcal septic shock reveal levels of Neisseria meningitidis (10 6-10 8 /mL) and endotoxin (10 1-10 3 EU/mL) in the circulation and organs, leading to acute cardiovascular, pulmonary and renal failure, coagulopathy and a high case fatality rate within 24 h. Objective: To investigate transcriptional profiles in heart, lungs, kidneys, liver, and spleen and immunostain key inflammatory cells and proteins in post mortem formalin-fixed, paraffin-embedded (FFPE) tissue samples from meningococcal septic shock patients. Patients and Methods: Total RNA was isolated from FFPE and fresh frozen (FF) tissue samples from five patients and two controls (acute non-infectious death). Differential expression of genes was detected using Affymetrix microarray analysis. Lung and heart tissue samples were immunostained for T-and B cells, macrophages, neutrophils and the inflammatory markers PAI-1 and MCP-1. Inflammatory mediators were quantified in lysates from FF tissues. Results: The transcriptional profiles showed a complex pattern of protein-coding and non-coding RNAs with significant regulation of pathways associated with organismal death, cell death and survival, leukocyte migration, cellular movement, proliferation of cells, cell-to-cell signaling, immune cell trafficking, and inflammatory responses in an organ-specific clustering manner. The canonical pathways including acute phase response-, EIF2-, TREM1-, IL-6-, HMBG1-, PPAR signaling, and LXR/RXR activation were associated with acute heart, pulmonary, and renal failure. Fewer genes were regulated in the liver and particularly in the spleen. The main upstream regulators were TNF, IL-1β, IL-6, RICTOR, miR-6739-3p, and CD3. Increased numbers of inflammatory cells (CD68+, MPO+, CD3+, and CD20+) were found in lungs and heart. PAI-1 inhibiting Brusletto et al. Transcriptional Profiles in MSS Organs fibrinolysis and MCP-1 attracting leukocyte were found significantly present in the septic tissue samples compared to the controls. Conclusions: FFPE tissue samples can be suitable for gene expression studies as well as immunostaining of specific cells or molecules. The most pronounced gene expression patterns were found in the organs with highest levels of Neisseria meningitidis DNA. Thousands of protein-coding and non-coding RNA transcripts were altered in lungs, heart and kidneys. We identified specific biomarker panels both protein-coding and non-coding RNA transcripts, which differed from organ to organ. Involvement of many genes and pathways add up and the combined effect induce organ failure.

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Section: Transcriptional Profiles In Heart Tissue Samplesmentioning

confidence: 98%

Extensive Changes in Transcriptomic “Fingerprints” and Immunological Cells in the Large Organs of Patients Dying of Acute Septic Shock and Multiple Organ Failure Caused by Neisseria meningitidis

Brusletto

Løberg

Hellerud

et al. 2020

Front. Cell. Infect. Microbiol.

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Pathophysiology, Treatment and Outcome of Meningococcemia: A Review and Recent Experience

Kirsch

Barton

Kitchen

et al. 1996

The Pediatric Infectious Disease Journal

205

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Frequency of myocarditis in cases of fatal meningococcal infection in children: observations on 31 cases studied at autopsy

Garcia

Castelo

Ramos

et al. 1999

Rev. Soc. Bras. Med. Trop.

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The frequency of myocarditis associated with meningococcal disease in children was reported only in two autopsied series (United States and South Africa). Here we report the frequency of associated myocarditis in 31 children who died of meningoccal infection at Hospital Infantil N.S. da Glória in Vitória, Espirito Santo State, Brazil. The diagnosis was confirmed by isolation of Neisseria meningitidis. At least three sections of fragments of both atria and ventricles were studied using the Dallas Criteria for the morphologic diagnosis of myocarditis. The mean age was 47.6 ± 39.8 months and the mean survival time after the onset of symptoms was 46.1 ± 26.5h (12-112h). Myocarditis was present in 13 (41.9%) patients, being of minimal severity in 11 cases and of moderate severity in 2 cases. There were no cases with severe diffuse myocarditis. The frequency of myocarditis was not influenced by sex, presence of meningitis, survival time after the onset of symptoms or use of vasoactive drugs. The frequency of myocarditis reported here was intermediate between the values reported in the only two case series published in the literature (57% in the United States and 27% in South Africa). Although our data confirm the high frequency of myocaditis in meningoccal disease, further investigations are necessary to elucidate the contribution of myocarditis to myocardial dysfunction observed in cases of meningococcal infection in children. Key-words: Myocarditis. Meningitis. Meningococcemia.Resumo A freqüência de miocardite associada à infecção meningocócica em crianças foi descrita apenas em duas series de casos autopsiados (Estados Unidos e África do Sul). Nessa comunicação relataremos a freqüência de miocardite em 31 crianças falecidas com doença meningocócica no Hospital Infantil N.S. da Glória em Vitória, E. Santo. O diagnóstico foi confirmado pelo isolamento da Neisseria meningitidis. Três secções ou mais, dos átrios e ventrículos, foram estudadas utilizando os critérios de Dallas para o diagnóstico morfológico de miocardite. A média de idade foi de 47,6 ± 39,8 meses e o tempo médio de sobrevida após o início dos sintomas foi de 46,1 ± 26,5 horas (12-112h). Miocardite foi identificada em 13 (41,9%) casos sendo de intensidade mínima em 11 e de intensidade moderada em dois casos. Nenhum paciente apresentou quadro morfológico de miocardite grave, difusa. A frequência de miocardite não foi influenciada pelo sexo, presença de meningite, tempo de sobrevida após o início dos sintomas ou pelo uso de drogas vasoativas. A freqüência de miocardite aqui apresentada é intermediária entre as únicas duas séries relatadas na literatura (57% nos Estados Unidos e 27% na África do Sul). Embora confirme a alta freqüência de miocardite na doença meningocócica, investigações são necessárias para elucidar a contribuição da miocardite para a disfunção miocárdica observada em casos de infecção meningocócica em crianças. Palavras-chaves: Miocardite. Meningite. Meningococcemia.

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Association of myocarditis and acute renal failure complicating meningococcal septicaemia

Cited by 4 publications

References 2 publications

Extensive Changes in Transcriptomic “Fingerprints” and Immunological Cells in the Large Organs of Patients Dying of Acute Septic Shock and Multiple Organ Failure Caused by Neisseria meningitidis

Extensive Changes in Transcriptomic “Fingerprints” and Immunological Cells in the Large Organs of Patients Dying of Acute Septic Shock and Multiple Organ Failure Caused by Neisseria meningitidis

Pathophysiology, Treatment and Outcome of Meningococcemia: A Review and Recent Experience

Frequency of myocarditis in cases of fatal meningococcal infection in children: observations on 31 cases studied at autopsy

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