A case report of acute mental behavioral abnormality resulting in death 1 year after rabies virus infectionLan Mou1 Hong Wang1 Jianhua Li1 Shikai Wang1*Department of Psychiatry, Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University, Huzhou, Zhejiang,313000, China*Corresponding author:Shikai Wang ORCID：0000-0002-2321-0524Huzhou Third Municipal Hospital, the Affiliated Hospital of Huzhou University.Huzhou, Zhejiang, China.E-mail addresses: wang-shikai@163.comKey Clinical MessageRabies is a fatal zoonotic disease. Acute mental behavioral abnormalities 1 year after infection with rabies virus are rare, but are medical emergencies that require prompt recognition.Keywords: rabies virus, mental behavioral abnormality,case report,death,acute medicine1.INTRODUCTIONRabies, a fatal zoonotic disease, is typically transmitted through the bite, scratch, or lick of an infected animal(Organization, 2018). Approximately 80% of cases present as encephalitic (rabid or typical) forms. When humans contract rabies, 50-80% develop typical symptoms such as hydrophobia and agoraphobia(Jackson, 2016). Unfortunately, the disease is usually incurable and ultimately fatal once clinical symptoms appear(Kumar et al., 2023). The glycoproteins on the surface of the rabies virus (RABV) genome have the ability to infiltrate large amounts of neuronal tissue in virtually any mammal(Fisher et al., 2018). After infecting peripheral nerves, RABV spreads through retrograde axonal transport to the central nervous system, where it replicates and spreads, eventually causing severe neurological symptoms and fatal outcomes(Yamaoka et al., 2013).The incubation period of RABV typically ranges from 20 to 90 days, although it can be as long as 20 years, depending on the viral entry site and viral load(Tajmalzai & Zarabi, 2024). Once the virus reaches the central nervous system, it often presents with neuropsychiatric symptoms. However, due to the lengthy incubation period and atypical symptoms, there is a risk of misdiagnosis in clinical settings, leading to delays in treatment. Here, we present a case of acute psychiatric behavioral abnormalities, along with hydrophobia, photophobia, and spasmodic seizures occurring a year after a dog bite, ultimately resulting in death.2. CASE HISTORY/EXAMINATION/PRESENTATIONThe patient, a 45-year-old male farmer, was involuntarily brought to the emergency department of a psychiatric hospital by his family while under restraint. He initially presented with symptoms such as insomnia, self-talk, inattention, and incoherent psychomotor arousal, accompanied by irritability, high agitation, and shouting. Over the course of two days, his symptoms escalated to include delusions of victimization and relationship, leading to aggressive behavior towards family members. However, the specific delusional content appeared inconsistent and varied upon further questioning. On physical examination, the patient exhibited normal bilateral pupils, equal in size and round, with a diameter of 3 mm, responsive to light reflexes, and no signs of facial palsy. Despite difficulties in cooperation during sensory and motor exams, he displayed strong spontaneous limb movements and normal muscle tone without any apparent abnormalities or signs of meningeal irritation. There were no signs of fever, seizures, nausea, vomiting, or hydrophobia upon admission. The patient denied any significant medical history. Results from electrocardiogram, electroencephalogram, and head and chest CT scans were all within normal limits.Routine laboratory tests revealed a white blood cell count of 22.14*10^9/L, with neutrophils at 20.49*10^9/L. Other blood cell counts, hemoglobin levels, and additional indexes were within normal limits. Furthermore, blood biochemical tests, including liver and renal function tests, electrolytes, glucose levels, and whole blood rapid C-reactive protein, all fell within the normal range.3.METHODS (DIFFERENTIAL DIAGNOSIS, INVESTIGATIONS AND TREATMENT)Given the patient’s unstable and aggressive behavior prior to admission, a diazepam injection of 10 mg IV was administered for rapid sedation, along with ribavirin 0.15 g for empirical antiviral therapy on the day of the emergency room visit. The patient’s symptoms showed slight improvement and there was no further aggressive behavior observed. However, later in the evening of the same day, the patient developed a low-grade fever, skin itching, hydrophobia, photophobia, intermittent and inconspicuous spasmodic episodes, and vomiting of coffee-like liquid. Upon further investigation into the patient’s medical history, it was revealed by the family and confirmed by neighbors that the patient had been bitten by a dog in the village a year prior and had not received rabies vaccination at that time.4.OUTCOME AND FOLLOW‐UPSubsequently, the patient was promptly transferred to the Infectious Diseases Hospital in the city. The following morning, the patient experienced a high fever, profuse salivation, and paroxysmal convulsions of the muscles throughout the body. His condition deteriorated rapidly, leading to his eventual death following cardiac and respiratory arrest. Viral antigens were identified in the saliva through direct immunofluorescence analysis5. DISCUSSIONRabies is a rare but fatal disease that causes approximately 59,000 deaths and more than 3.7 million disabilities each year, particularly prevalent in developing countries(Hampson et al., 2015). In China, around 40 million people are bitten by dogs annually(Shen et al., 2023; Tu et al., 2018), with dog-associated RABV being the primary pathogen responsible for human rabies cases in inland provinces of China(Wang et al., 2014).Its typical symptoms usually last no more than a month and can be divided into three main phases(Depani et al., 2012; Depani et al., 2013; Wang et al., 2015) : (1) In the prodromal phase, most patients experience fever, some may have other flu-like symptoms, and many report abnormal sensations around the wound, such as numbness, pain, itching, and ants. (2) During the excitatory phase, patients become hydrophobic and may experience spasms of the pharyngeal muscles, difficulty breathing, urination and defecation issues, excessive sweating, and saliva retention. (3) In the paralytic phase, the patient becomes quiet and develops flaccid paralysis, especially in the extremities; involvement of facial muscles can lead to irregular eye movements, jaw tension, mouth drooping, and lack of facial expression. The most common symptoms include aggression, hydrophobia, fear of wind, and progressive paralytic paralysis(Carrara et al., 2013; Gilbert et al., 2015; Tian et al., 2019).The time interval between exposure to RABV and the onset of symptoms typically ranges from 3 weeks to 4 months(Laryea et al., 2017). In the case of our patient, the acute onset of the disease one year after the dog bite may be attributed to the slow replication of the virus and the establishment of latent infection following the initial exposure. It is possible that the virus was reactivated due to neurotropic viral infection at a later time(Amoako et al., 2021).Before the development of typical symptoms of aggression and hydrophobia, the emergency examination did not reveal any obvious abnormalities, except for an abnormally elevated blood image. The diagnosis was confirmed post-mortem only through the detection of rabies virus antigen in saliva via direct immunofluorescence. The patient initially exhibited acute psychobehavioral abnormalities, characterized by psychomotor instability and psychotic symptoms, indicative of a manic rabies type. Research has shown that patients with manic rabies experience more severe damage to pyramidal neuronal cell bodies in the hippocampal corners compared to those with paralytic rabies(Shuangshoti et al., 2013). Additionally, various components of the hippocampus, where limbic symptoms are prominent, are more impacted(Shuangshoti et al., 2016). The progression of symptoms in this case appears atypical, with a prodromal phase featuring insignificant symptoms, followed by a rapid onset of impaired consciousness and death during an excitatory phase, skipping the paralytic phase typically observed.Throughout the course of the disease, the case was marked by psychiatric symptoms. The patient exhibited nonsensical speech and provided unintelligible answers, complicating clinical questioning and hindering a thorough history-taking process. Moreover, the patient experienced an unusually long incubation period for rabies, atypical symptoms in the prodromal stage, and no apparent abnormalities in the EEG and CT scans of the skull. These factors, coupled with healthcare workers’ limited familiarity with the clinical presentation of rabies, the family’s initial denial of a history of dog injury, and the absence of further cranial MRI examination, were the primary contributors to the misdiagnosis. Clinicians should enhance their understanding and prioritize differential diagnosis.6.CONCLUSIONIt is imperative to heighten awareness of rabies, particularly its psychiatric behavioral manifestations, as delayed or incorrect diagnosis can lead to crucial treatment opportunities being overlooked. Therefore, psychiatrists should consistently consider rabies as a differential diagnosis, especially for new patients hailing from rural regions.AUTHOR CONTRIBUTIONSLan Mou: Data curation; Project administration;Investigation; Visualization;writing – original draft.Hong Wang,Jianhua Li: formal analysis; supervision. Shikai Wang: Conceptualization; supervision; writing – review and editing.FUNDING INFORMATION None.CONFLICT OF INTEREST STATEMENT None declared.CONSENT Written informed consent was obtained from the patient’s relative.ReferencesAmoako, Y. A., El-Duah, P., Sylverken, A. 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