A 70-year-old male was admitted to hospital on January 12, 2022, with vomiting for five days and losing consciousness for three days as the main manifestations. Before admission, the patient vomited gastric contents accompanied by watery diarrhea due to the consumption of uncleaned food. Due to the absence of abdominal pain, fever, headache and dizziness, the patient was not concerned about his health. The patient presented to a local hospital for vomiting and watery diarrhea three days before admission. He was provided symptomatic treatment for acute gastroenteritis and discharged after the improvement of symptoms. Two days before admission, the patient suffered from a sudden coma after drinking water, which lasted approximately 10 minutes. The patient was then admitted to the local hospital. Clinical examination showed a blood pressure of 60/50 mmHg, and magnetic resonance (MR) indicated multiple cerebral ischemias. Anti-infection and fluid rehydration treatments were administered on this basis. During the treatment, the patient suffered from frequent comas (1–2 minutes each time). The patient presented with renewed vomiting and loss of consciousness, followed by urgent transfer to our hospital for further diagnosis and treatment. On admission, the patient's heart rate was 45 beats/min, his blood pressure was 76/42 mmHg, and SpO2 was 85. He was provided emergency treatment with orotracheal intubation with mechanical ventilation. The patient had a history of hypertension for 13 years and his blood pressure was controlled by regular oral administration of 5 mg qd amlodipine besylate. There was no other notable personal or family medical history.
Physical examination after admission indicated that the patient’s temperature was 37.4℃, heart rate was 96 beats/min (orotracheal intubation with mechanical ventilation: p-CMV, frequency, 10 beats/min, pressure support, 10 cmH2O, positive end-expiratory pressure, 8 cmH2O, and oxygen concentration, 40%), and blood pressure was 148/77 mmHg (norepinephrine pumped at 0.3 µg/kg/min). The patient was in a sedative and analgesic state. The bilateral pupils were round and equal in size, while pupillary reactions to light were existent. The patient’s breathing sound was rough. There were no rhonchi or moist rales and breathing was free of pathological murmurs. However, an irregular cardiac rhythm was observed, and the abdomen was soft. A scar was observed on the right hand (Fig. 1) and no edema was observed on either of the lower extremities.
The black arrows indicate the scar on the right hand of the patient, which was identified during the physical examination performed after the patient’s admission to hospital.
Laboratory testing was also performed. Routine blood tests showed that the white blood cell (WBC) count was 11.7×109 /L, and the neutrophil ratio was 82.9%. Blood gas analysis (BG) revealed that the pH was 7.26, and the partial pressures of CO2 and oxygen were 32.3 mmHg and 207.9 mmHg, respectively. The concentrations of bicarbonate and lactate were 22.3 mmol/L and 1.1 mmol/L, respectively. Moreover, biochemical examinations indicated that sodium, calcium, phosphorus, and uric acid levels were 155.5 mmol/L, 1.91 mmol/L, 2.09 mmol/L, and 657.7 µmol/L, respectively. Liver function analyses revealed that the concentrations of total bilirubin, direct bilirubin, indirect bilirubin, and creatinine were 36.5 µmol/L, 16.5 µmol/L, 20 µmol/L, and 253 µmol/L, respectively. Furthermore, we learned from the patient's CT scans that there were lacunar cerebral infarcts in bilateral basal ganglia and brain atrophy. We noticed chronic bronchitis and emphysematous on both sides, and a small amount of bilateral fluid accumulation in the chest cavity. Aortic and coronary atherosclerosis and severe pneumatization of the transverse and ascending colon were also observed.
The initial diagnosis was septic shock caused by an intestinal infection. Therefore, the patient was treated with mechanical ventilation, blood pressure maintenance, fluid replenishment and expansion, electrolyte balance, acid-base equilibrium maintenance, anti-infectives, and other supportive treatments. Pulse index Continuous Cardiac Output (PiCCO) was also used to monitor the patient's hemodynamics. Electrocardiography monitoring exhibited frequent sinus arrest and third-degree atrioventricular block within 12h of admission, with no obvious abnormality observed on echocardiograms (Ao Diam: 27 mm, LA Diam: 36 mm, LVIDd: 45 mm, LVIDs: 32 mm, IVST: 8 mm, LVPWT: 8 mm, EF: 57%, TAPSE: 19 mm). Analyses of myocardial markers demonstrated that the concentrations of hypersensitive troponin I, myoglobin, and creatine kinase isoenzyme were 1.9391 ng/mL, 186.3 ng/mL, and 8.9 ng/mL, respectively. Based on all such findings, the patient was then considered to have Adams-Stokes syndrome caused by frequent sinus arrest and third-degree atrioventricular block, and was immediately commenced on noninvasive transcutaneous cardiac pacing (pacing rate, 60 ppm; output current, 10 mA). On the second day of admission (2022-01-13), the patient's routine blood testing displayed a WBC count of 11.7×109 /L, and the percentage of neutrophils was 82.9%. Therefore, 4.5 g q8h of piperacillin tazobactam was administered for anti-infection therapy.
The patient's blood and BALF were collected for mNGS detection (Dinfectome Inc., Nanjing, Jiangsu Province, China). Within 24 h, mNGS generated a total of 24,253,153 single-end reads in the genomic DNA of the BALF, of which 124 reads were Rabies lyssavirus, with a genome coverage of 92.18% (Fig. 2). No Rabies lyssavirus DNA was detected in the blood sample (Table. 1). Through questioning the patient's wife, it was learned that the patient was bitten by a dog on the right hand two months prior and had not been vaccinated against rabies. Based on the patient's history, the clinical manifestations, and the mNGS results, the patient was clinically diagnosed with atypical rabies with Adams-Stokes Syndrome. The patient developed generalized convulsions and was administered sodium valproate via injection (0.4 g q8h) and oral levetiracetam (0.5 g bid). The 24-Holter monitor showed an average heart rate of 87 bpm, the standard deviation of NN intervals (SDNN) of 72 ms, ST change, 411 premature atrial beats and three PVC beats, with 122,004 normal beats. The myocardial markers hypersensitive troponin I and myoglobin were also detected at 0.3573 ng/mL and 113.5 ng/mL, respectively. Intravenous injection of sodium creatine phosphate (1 gevery 12 h) was administered to protect the myocardium. On the fourth day of admission (2022-01-15), the patient developed bulbar conjunctival edema. The lumbar puncture results were as follows: (1) pressure: 200 mmH2O, (2) total white blood cells: 2×106/L, (3) chlorine: 141.2 mmol/L, (4) glucose: 5.57 mmol/L, and (5) protein: 0.62 g/L. The coagulation function findings were as follows: (1) prothrombin time (PT): 12.3 sec, (2) activated partial thromboplastin time (APTT): 33.3 sec, and (3) fibrinogen (FIB): 3.92 g/L. Hence, 125 mL of mannitol q8h was added to reduce intracranial pressure, and 500 mL of virus-inactivated plasma was added to supplement coagulation factors. However, the prognosis was poor, and multiple organ failures occurred. The patient's family decided to terminate the treatment on the 5th day of admission (2022-01-16), and the patient was discharged voluntarily. The patient died on the same day as discharge.
The mNGS sequence was aligned to the best matching rabies virus genome (NCBI-accession: JQ970483.1). The total genome coverage was 92.18%.
Table 1
Sample type | Detection method | Species | Reads | Relative abundance (%) | Coverage (%) |
---|
Bronchoalveolar lavage fluid | Metagenomic | Streptococcus pneumoniae | 98 | 0.78 | 5.43 |
Streptococcus pseudopneumoniae | 25 | 0.2 | 5.51 |
Candida albicans | 139 | 92.05 | 0.06 |
Metatranscriptomic | Streptococcus pneumoniae | 9 | 0.11 | 0.49 |
Streptococcus pseudopneumoniae | 3 | 0.04 | 0.45 |
Rabies lyssavirus | 127 | 95.38 | 92.18 |
Blood | Metagenomic | – | – | – | – |
Metatranscriptomic | – | – | – | – |