The first case report of acute myocardial infarction in young adult caused by scrub typhus

Rationale: Scrub typhus is a zoonotic disease caused by Orientia tsutsugamushi, a gram-negative intracellular bacterium and endemic in Asia-Pacific area. Acute myocardial infarction after Oricntia tsutsugamushi infection was rarely reported, and young adult was not reported. Patient conerns: A 33-year-old man came to the emergency complained with chest tightness and fever for 4 days. Diagonoses: After Weil-Felix agglutination test (titer 1:160) twice, scrub typhus was diagnosed. Interventions: After treating with a hormonotherapy, antibiotic and ventilator-assisted ventilation, his chest tightness was mild lessened with normal breath and body temperature. However, an emergent coronary angiography performed unnormal, then a percutaneous coronary intervention was realized with the implantation of a stent. Outcomes: After the surgeon, his chest tightness was totally released, and he was discharged. Lessons: Our case was the first report of young adult acute myocardial infarction after O tsutsugamushi infection and we tried to figure out the potential mechanism and how to deal with.


Introduction
Scrub typhus is a vector-borne zoonosis caused by the organism Oricntia tsutsugamushi, [1] and endemic in Asia-Pacific area. [2,3]The most typical symptoms in adults were fever and headache, and fever in pediatric. [3,4][7] Here we reported a young man with acute myocardial infarction (AMI) after O tsutsugamushi infection and tried to figure out the potential mechanism and how to deal with.

Case presentation
A 33-year-old man came to the emergency on 6th April 2020 with chest tightness and fever (37.5°C-38.8°C)for 4 days.Laboratory data revealed WBC 16.88 × 10 9 /L, CRP 37 mg/L, D-dimer 4.7 mg/L.Chest CT scan showed diffuse patches in bilateral lungs, clearly low lobe.ECG performed negative.He denied hypertension, diabetes, smoking history, and family history of hereditary diseases.After several hours therapy, his chest tightness worsened and dyspnea was present, so he was sent to ICU.At admission, physical examination was performed with rough breath sound with moist rale, and an eschar with 3 to 5 cm diameter sized was found in the right lower limb (Fig. 1).Cardiac enzymes were seriously raised, D-dimer 4.7 mg/L, CK-MB > 300 ng/mL, and troponin T 1166 pg/mL.ECG showed ST elevation in V 2-4 .The patient was treated with cardiopulmonary supports (endotracheal intubation, and mechanical ventilation), anti-infection (Cefazolin sodium i.v., and Vancomycin i.v.) and anticoagulation (low molecular weight heparin s.c.).According to the second time Weil-Felix agglutination test (titer 1:160) positive result, scrub typhus was certainly diagnosed, and after 7 days oral minocycline his chest tightness was mild lessen with normal breath and body temperature.Cardiac enzymes decreased D-dimer 6.56 mg/L, CK-MB 2.1 ng/mL, and TnT 204.1 pg/mL.However, ECG showed sinus tachycardia, ST elevation in V 2-6 , and abnormal Q wave in V 2-5 (Fig. 2).An emergent coronary angiography was performed with a 50% stenosis in the proximal segment and 85% to 90% stenosis in the middle segment of the left

The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.anterior descending artery, and a thrombus can be visible in the middle segment (Fig. 3A).A percutaneous coronary intervention of the left anterior descending artery was realized with the implantation of a stent (Fig. 3B).After percutaneous coronary intervention, his chest tightness was totally released, and he was discharged.The patient has provided informed consent for publication of the case.

Discussion
O tsutsugamushi infection as well as other rickettsial infections would involve several organs including lung, liver, heart, and brain.It was supposed that organ injury results from microvascular dysfunction, which was caused through endothelial cells (ECs) infection and inflammation.Moreover, ECs   inflammation was considered as the pathogen, and leaded to endothelial and platelet activation that caused platelet adhesion, microvascular thrombosis, and dysfunction, finally multi-organ failure. [8]Recent research revealed furthermore mechanism of ECs malfunction in O tsutsugamushi infection. [9,10]Additionally, the immune-mediated host response combined with humoral, and cell mediated immunity also contributed to the pathology.Ge H reported that parts of interleukins, chemokines, and growth factors were highly induced early post O tsutsugamushi infection, whereas interferon-α2 was profoundly down-regulated. [10]Wangsanut T reported that O tsutsugamushi specifically stabilized p105 to inhibit the canonical NF-κB pathway in vitro. [11]cute bacterial and viral infections were tightly associated with an increased risk of myocardial infarction. [12]owever, AMI following O tsutsugamushi infection was rarely reported, and firstly reported by South Korea counterpart in 2007. [13]Scrub typhus patients autopsied revealed that most case hearts were pale, soft, flabby, or slightly friable, only 2 case hearts contained small atheromatous plaques in the proximal portions of coronary arteries. [14]Cerebral, splenic infractions caused by O tsutsugamushi infection were also reported in recent years. [15,16]So, it was seemed that O tsutsugamushi infection would rarely induce large vessel infarction in brain, spleen, and heart, probably involved via EC inflammation or immune-mediated host response.More clinical research was required to figuring out the exact relationship between O tsutsugamushi infection and large vessel infarction.In this case, we reported AMI caused by O tsutsugamushi infection in a young adult (aged <35) firstly in the world overall.The young man denied hypertension, diabetes, and smoking history, all the high-risk factors of AMI were excluded.Therefore, his AMI was most probably caused by O tsutsugamushi infection.
Cardiac injury was commonly seen in patients with O tsutsugamushi infection, presenting as NT pro-BNP, troponin T, and CK-MB levels elevated as well as ejection fraction reduced in echocardiography, and ECG abnormalities. [6,17]Myocardial injury, myocarditis, and left ventricular systolic disfunction were frequently recognized and associated with increased morbidity but not mortality. [18]Due to this phenomenon, AMI as a rare cardiac disease in scrub typhus was easily misdiagnosed.According to this spot, we supposed the operation of coronary computed tomography angiography or digital subtraction angiography as early as possible would benefit the patients with cardiac manifestations of O tsutsugamushi infection.
O tsutsugamushi infection might induce high morbidity and mortality despite low-cost and high-effect antibiotic therapy such as doxycycline, due to delayed recognition and diagnosis.Weil-Felix test first described in 1916, was a test used in the diagnosis of rickettsial infection world widely.However, IgM ELISA became available for scrub typhus diagnosis due to its better specificity and sensitivity. [19]Nowadays, novel diagnosing methods such as IgM immunofluorescence assay (IFA), metagenomic next-generation sequencing (mNGS) were available.IFA was considered as the gold standard diagnostic test instead of IgM ELISA. [20]mNGS performed better than conventional clinical methods to early diagnose scrub typhus. [21]In this case, Weil-Felix test was performed twice without IgM ELISA or IgM IFA, and the patient refused mNGS due to high cost.Although a typical skin change was present in this case, the recognition and diagnosis were delayed due to the conventional diagnosis methods, and novel clinical methods were required for early diagnosis.
Our study was supported by Nanjing TCM Young Talent Training Program.

Figure 1 .
Figure 1.(A) A eschar was seen on the patient's lower limbs.(B) Pathological examination of skin biopsy specimens of the lower limbs showed mild hyperplasia of surface squamous epithelium and small vessels in the superficial dermis, with focal lymphocyte infiltration, and hyperplasia of collagen fibers in the dermis.

Figure 3 .
Figure 3. (A) Coronary angiogram demonstrated 50% stenosis in the proximal segment of LAD and 85-90% stenosis in the middle segment, showing a thrombus shadow.(B) Three stents were placed in the near and middle segment of LAD.LAD = left anterior descending artery.