LAUSR

To the editor, The world has witnessed the emergence of mpox virus (mpoxv) from multiple countries in 2022. The mpox case fatality rate of 3%−6% is far lower than smallpox (30%). Till now, India has reported 25 confirmed mpox cases from Kerala (n = 10) and New Delhi (n = 15) during July 2022 to February 2023. Here, we report the first fatal mpox case imported from UAE to Kerala, India. On July 27, 2022, a 22‐year old apparently immunocompetent male was admitted in an unconscious state to a private hospital in Kerala following single episode of acute‐onset generalized tonic‐clonic seizures with fever. The case details were taken from the hospital's medical record and family members provided the history. As the patient was in comatose stage, gaps in history provided by relatives could not be verified. He developed fever, and headache on July 15 while in UAE followed by painful purulent right inguinal lymphadenopathy and sought medical care on July 19. He was partially relieved of his symptoms and returned from UAE on July 21. Considering the worsening of pain in right inguinal region, he consulted a surgeon on July 25 in Kerala and was diagnosed with hidradenitis suppurutiva. He continued to report fatigue and low‐ grade fever but no persistent headache, altered sensorium, loss of appetite, or weight. Two days later, the patient was brought unresponsive to the emergency. On evaluation, his vitals were stable with no signs of meningeal irritation; however, physical exam identified right inguinal lymphadenopathy with abscess formation and a single healed scrotal lesion with no exanthemas. Considering the unresponsive state, encephalitis was suspected and the patient was shifted immediately to negative pressure single‐patient isolation intensive care unit. The Glasgow coma scale score was 7 [eye: 01; verbal: 02; motor: 04]. The brain magnetic resonance imaging (MRI) revealed diffuse cerebral edema, altered signal intensity (FLAIR hyperintensity with mild restricted diffusion) in bilateral cerebral cortical and subcortical regions, bilateral caudate nucleus, putamen, posterior genu of corpus callosum. The electroencephalogram (EEG) was suggestive of generalized cerebral dysfunction. The MRI, EEG, and cerebrospinal fluid (CSF) findings were suggestive of an acute meningoencephalitis (Table 1). Serological tests for HIV, hepatitis B, hepatitis C, and syphilis were negative. At presentation, he had neutrophilic leucocytosis with normal hepatic function. Over the next 48 hours, he developed coagulopathy and acute kidney injury (Table 1). Myocarditis was ruled out by echocardiogram and cardiac biomarkers. The presence of inguinal lymph nodes with abscess, along‐with the neuroimaging and CSF profile suggestive of meningoencephalitis, he was empirically started on anti‐tubercular drugs, antibiotics to cover neurobrucellosis and acyclovir. On July 28, he developed features of worsening cerebral edema and was intubated and mechanically ventilated. Despite anti‐cerebral edema measures, he progressed to brainstem dysfunction and succumbed on July 30, 2022. Just before his death, the relatives informed the result of mpox positivity tested on July 19 at UAE. With this new information, the clinical specimens that is, oropharyngeal swab (OPS)/nasopharyngeal swab (NPS), plasma, and serum collected on July 30 were referred to ICMR‐National Institute of Virology for mpoxv diagnosis by real time PCR. The mpoxv DNA was only detected in the OPS/NPS (1.7 × 10 copies/mL). The CSF specimen was unavailable for testing to confirm encephalitis associated with mpoxv. The next generation sequencing on the OPS/NPS specimen [GISAID accession no. EPI_ISL_15008573] aligned 91.2% to the mpoxv genome belonging to A.2 lineage of clade IIb as observed in other mpox cases from India. Encephalitis had been reported previously as the complication of mpox, leading to fatality. However, encephalitis associated with mpoxv in immunocompetent patients is rarely reported and could be either due to direct infection or autoimmune encephalitis like MOGAD [myelin oligodendrocyte glycoprotein antibody associated disease] with viral infections. The clinical and neuro‐imaging features in this case are more in favor of direct mpoxv encephalitis than MOGAD. However, MOGAD was not conclusively rule out considering the unavailability of the serum and CSF specimens for further testing. All other usual causes of encephalitis had been ruled out by Film Array Meningitis/Encephalitis panel (Biofire Diagnostics) and additional testing for Japanese encephalitis virus, West nile virus, and Nipah virus (Table 1). In this case, apart from a doubtful healed scrotal lesion and lymph node abscess, no other skin lesions were present. This is the first fatal mpox case reported from India which highlights the importance of maintaining a high index of suspicion to diagnose mpox in atypical presentations, and in exanthematous fever with epidemiological linkage. The OPS/NPS and urine specimens should be considered as the critical specimens for mpoxv diagnosis in cases with no active skin lesions.