The past and present of endocarditis——The application of mNGS in infective endocarditis

The occurrence of endocarditis has been premeditated for a long time

Recently, today's headlines, Sohu and other major news websites also reported a "strange" news, "men don't brush their teeth before going to bed, infected with endocarditis". The news reported that Mr. LV, who went to the stomatology department of Hongqi hospital, often worked overtime late at night due to his busy work. He was unable to do the basic homework of brushing his teeth before going to bed, which eventually led to endocarditis. This news has aroused the heated discussion of the majority of netizens. A seemingly ordinary bad habit can cause such terrible consequences. Will everyone, like Xiaobian, crazy carry out "oral cleaning" these two days. So what is endocarditis? Why not brush your teeth may cause endocarditis? Today, I'll make it up for you to popularize science.

endocarditis

Endocarditis, which can be popularly understood as "inflammation" of the endocardium of the heart, can be divided into non infective endocarditis and infectious endocarditis (ie) caused by pathogens. Noninfectious endocarditis is caused by trauma, local blood vortex, circulating immune complex, aseptic platelet and fibrin thrombosis on heart valve and adjacent endocardium, which will lead to a series of clinical symptoms. Infective endocarditis is due to the failure of the body to clean up in time after various pathogens enter the blood, the pathogens live and reproduce in the heart, invade the surrounding cells, lead to the shuttle blockage of thrombotic particles in the blood vessels, and finally cause endocardial inflammation. The incidence rate of IE is about 3-10 cases per year and 100 thousand cases of [1], and the mortality rate is as high as 40%[2].

Figure 1 endocarditis (picture from network invasion and deletion)

Clinical symptoms

Endocarditis is often accompanied by a series of clinical symptoms and peripheral signs. Common symptoms include: flu like symptoms, such as fever and chills, heart murmur, fatigue, joint and muscle pain, night sweats, shortness of breath with chest pain, swelling of feet, legs or abdomen, etc; Rare symptoms include unexplained weight loss, blood in urine, tenderness of spleen, Janeway's lesion, Osler's section and ecchymosis.

Figure 2 peripheral signs of infective endocarditis

A. Osler's nodes [3]

B. Janeway lesions [3]

C. Roth's spots [4]

D. Conjunctival hemorrhage [5]

Pathogenesis

The pathogenesis of IE can be divided into four consecutive events and four stages.

4 consecutive events

1. Non bacterial thrombotic vegetations, endothelial cell damage, fibrin and platelet deposition;

2. Local release of pathogens into the blood circulation;

3. Pathogens attached to vegetations, followed by fibrin and platelet aggregation, covered their colonies and became the basis of vegetations;

4. So that pathogens can grow and reproduce here.

After the above four consecutive events, the infection focus was formed.

Since then, the infection focus continued to evolve into the following

4 processes

1. When the vegetations break locally, they release pathogens into the blood circulation, resulting in transient bacteremia;

2. Local invasion of vegetations containing pathogens leads to abnormalities of intracardiac conduction system, annular abscess, pericarditis, aortic sinus aneurysm and valve perforation;

3. The infected vegetative fragments fall off and cause peripheral embolism of systemic and pulmonary circulation;

4. The existing antibodies in blood form immune complexes with pathogen antigens. In cases of infective endocarditis, Streptococcus and Staphylococcus are the main pathogenic bacteria, accounting for about 80% of all pathogenic bacteria [6].

Table 1 pathogenesis of infective endocarditis

Note: "HACEK" bacterial group is composed of five genera, and H represents Haemophilus,

A represents Actinobacillus, C represents cardiobacterium,

E stands for Eikenella and K for Kingella [7]

Detection of pathogens

Infective endocarditis is a relatively high mortality rate. Epidemiological studies show that its incidence rate is increasing year by year. Despite early diagnosis and surgical intervention, the incidence rate and mortality rate have not been improved in the past 20 years. Therefore, timely determination of the etiology and scientific and effective diagnosis of infectious endocarditis is of great significance for the intervention of IE.

The detection of common pathogenic microorganisms mainly depends on the culture method, but the culture cycle is long, and it can not cover the species such as viruses, fungi and parasites, which has some limitations. Metagenomic next generation sequencing (mngs), as a new auxiliary diagnostic technology, does not rely on prior information, does not need doctors' prediction, and does not rely on culture. It can detect all sequences of pathogenic microbial genome, and can find new or rare pathogens. It is suitable for scientific research and clinical application of pathogens with unknown causes, It has obvious advantages in opportunistic infection and mixed infection. This new method is changing the way clinicians diagnose and treat infectious diseases, and it can also make the diagnosis and treatment of IE patients and the rapid intervention treatment possible.

Mngs helps diagnose endocarditis pathogens

2013

Atsuko [8] et al. Applied mngs technology to the pathogen detection of ie. the researchers performed routine culture and mngs detection on the valve tissues of 3 patients with ie at the same time. The results showed that the detection results of mngs were highly consistent with the positive results of culture. In the samples with negative culture results, the pathogens detectable by mngs were verified to be true by Gram staining, The reliability of mngs method in IE pathogen detection is proved. Cheng [9] et al. Tested 44 patients with IE with mngs and compared them with traditional detection methods. They found that the sensitivity, specificity, positive predictive value and negative predictive value of mngs were 97.6%, 85.7%, 97.6% and 85.7%, blood culture was 46.2%, 100%, 100% and 12.5%, flap membrane culture was 17.1%, 100%, 100% and 17.1%, and valve Gram staining was 51.4%, 100%, 100% and 26.1%. The results show that mngs not only continues the same high specificity and positive predictive value as traditional detection methods, but also makes up for the shortcomings of low sensitivity and negative predictive value of traditional detection methods. It can be seen that mngs is expected to become an efficient detection tool for IE diagnosis and treatment.

May 2019

Kondo [10] et al. Reported a successful application of mngs in IE direction. A 29 year old male presented with intermittent fever, night sweats and weight loss for 18 months. The patient has a history of tetralogy of Fallot (TOF) and has undergone many heart operations, including Blalock shunt 7 days after birth, repair after 3 years old, pulmonary valve replacement (PVR) in 2006 and bioprosthetic PVR in 2014. After the operation, the patient went to Pakistan, Thailand, Laos and Myanmar, and drank unpasteurized milk in the Midwest of the United States. Initial blood culture and fourth generation HIV screening were negative. Subsequently, the patient also brought the case information related to the PVR operation performed by the hospital in 2014, warning that there may be Mycobacterium chimera infection. Other possible pathogens include Bartonella henselae, Brucella and Coxiella burnetii. The clinician tested the plasma samples of the patient for mngs. According to the test results, the patient was diagnosed as endocarditis caused by C. burnetii infection. Subsequently, hydroxychloroquine (200 mg orally every 8 hours) and doxycycline (100 mg orally every day) were used for treatment. After 4 weeks of treatment, the clinical symptoms of the patient completely subsided, and finally PVR and graft exchange were successfully carried out. Through this case, the researchers believe that mngs sequencing of cfdna in plasma has more significant advantages than traditional clinical detection methods.

First, mngs can detect all pathogens such as bacteria, fungi, parasites and viruses in one experiment, reducing the need for specific detection of a large number of pathogens. Secondly, the detection cycle is short, which is convenient for early treatment. Specimen collection is a minimally invasive (venipuncture) method, which can reduce invasive operations such as tissue biopsy and reduce the pain of patients.