INTRODUCTION Human herpesvirus-6 (HHV-6) is a double-stranded DNA virus belonging to the Roseolovirus family. The sixth illness, or exanthem subitum, is the more well-known HHV-6 symptom. After primary infection, HHV-6 has the potential to become reactivated in the future. HHV-6 has been linked to encephalitis and meningoencephalitis in adult populations, particularly in the immunocompromised, in addition to other disseminated disorders. Meningitis, epilepsy and other neurological symptoms have been noted in both immunocompetent and immunocompromised people, including febrile seizures.[1] In our case, a young immunocompetent female patient was one of the few to have HHV-6 encephalitis. The diagnosis was verified by quantitative polymerase chain reaction (PCR), and the patient responded completely to ganciclovir without experiencing any more complications. CASE REPORT A 27-year-old Indian female presented with fever for 5 days, abnormal body movement, jerky movement of legs and frothing from the mouth for 1 day. There was no history of recent travel or new medications. Her vaccination status was up to date. On examination, the patient's temperature was 38.6°C, blood pressure was 90/62 mmHg, heart rate was 110 beats/min and saturation SPO2 was 98% on room air. Initial fingerstick blood glucose at the bedside was 105 mg/dL. She had an 11 on the Glasgow Coma Scale, was agitated and uncooperative during the history and examination, and was solely aware of herself and time. Her appearance was scruffy, and his mucous membranes were dry. No notable findings of erythematous scrapes lesions were found on examination. No symptoms of meningeal inflammation or generalised or specific neurological impairments were present. Initial laboratory examinations were remarkable for leucocytosis (20.2 × 103/mm3), blood urea nitrogen 42 mg/dL and creatinine 0.96 mg/dl. The electrocardiogram showed sinus tachycardia with exceptional results. Both chest X-ray and computed tomography of the brain and cervical spine without contrast were normal. She received oral lorazepam and IV dexamethasone out of concern for possible meningitis/encephalitis, and acetaminophen for the fever while in the emergency department. A full septic workup was performed on the patient, which included blood cultures, lumbar puncture at the bedside, empiric IV acyclovir, as well as vancomycin and ceftriaxone until the results of the cerebrospinal fluid (CSF) analysis were available. A specific gravity of 1020, colourless, clear appearance, normal glucose (56 mg/dL) and increased protein (69 mg/dL) were all found in the CSF examination. She had CSF cultures performed for common bacteria, fungi and mycobacteria, as well as CD4+ T cell counts. Examinations of the CSF samples for common bacteria, fungi and parasites were negative. The polysaccharide cryptococcal capsular antigen in the CSF was negative. The definitive diagnosis was made by DNA detection of HHV-6 in CSF by multiplex PCR by TRUPCR Neuro Panel kit [Figure 1]. The TRUPCR Neuro Panel kit is a multiplex PCR device that amplifies and detects the genomes of Herpes simplex-1 (HSV-1) and 2 (HSV-2) and herpes varicella-zoster, human cytomegalovirus, human Epstein–Barr virus HHV-6 and 7, human parechovirus, human parvovirus B19 human adenovirus and enterovirus. To continue treating viral encephalitis, it was decided to move the patient to the medical intensive care unit. Her regimen was expanded to include maintenance fluids with normal saline and IV ganciclovir 5 mg/kg daily. Throughout his hospital stay, basic metabolic tests and a complete blood count were followed, and she was kept on lamotrigine 100 mg twice a day. An electroencephalogram investigation was done by neurology, and it revealed multiple electrographic seizures as well as an epileptogenic lesion in the left temporal area.Figure 1: Graph of positive human herpesvirus-6 on reverse transcription-polymerase chain reactionFurther, COVID-19 nasopharyngeal swabs came out negative. CSF acid-fast bacilli, peripheral blood cultures and CSF cultures all showed no growth during hospitalisation or 8 weeks after admission. The patient's encephalitis had a favourable clinical response 1 week later. She was discharged on lamotrigine 50 mg twice daily and IV ganciclovir 5 mg/kg daily, which was changed to oral valganciclovir 450 mg for another two weeks. One week after being discharged, a follow-up laboratory test revealed significant levels of HHV-6 immunoglobulin G (IgG) antibodies that had been undetectable upon admission to the hospital. DISCUSSION HHV-6 infections mostly affect the extremely young, typically those under 3 years of age; HHV-6 is well known for being the cause of roseola infantum (also known as exanthema subitum or sixth illness).[1] Numerous studies have demonstrated that due to increased cytokine release, primary HHV-6 infection in children may be compounded by neurological sequelae.[2] Encephalitis, acute necrotising encephalitis, acute encephalopathy with biphasic seizure syndrome and/or demyelinating illness are some of these consequences.[3] Although HHV-6 encephalitis can occur in adults as a primary infection or reactivation, it frequently affects immunocompromised, HSCT patients and recipients of solid organ transplants. HHV-6 meningoencephalitis in immunocompetent individuals can lead to lasting complications. These include seizures and epilepsy, cognitive impairment affecting memory, behavioural changes, motor dysfunction and an increased risk of chronic fatigue syndrome. Recurrent episodes and reactivation of HHV-6 may worsen neurological complications over time. These long-term sequelae significantly impact an individual's quality of life, affecting cognition, motor skills and emotional well-being. Ongoing research and multidisciplinary clinical management are crucial to understanding and addressing these enduring effects. Our patient, a 27-year-old adult female, did not fit into any of these three groups because she was immunocompetent and had never undergone HSCT or an organ transplant. Pathophysiologically, HHV-6 can infect a host in three different ways: primary infection, latent infection reactivation and activation of chromosomally integrated HHV-6 DNA (ciHHV-6). Through homologous recombination, the viral genome is incorporated into the subtelomeric region of the host's chromosomes to form CiHHV-6, which can be passed on to offspring and harm every cell in the child's body.[4] A patient's medical management and therapy may be greatly influenced by knowing if they have ciHHV-6, which affects between 0.2% and 1% of the population in affluent nations.[4] The significance of HHV-6 DNA being present in CSF has recently come under examination, and rightfully so.[1] This is because the diagnosis of a primary, actively replicating infection was given in error.[1] when viral DNA was found in the CSF of ciHHV-6-afflicted people. Numerous testing techniques have been employed to aid in the diagnosis of HHV-6 infection to avoid misdiagnosis, but quantitative PCR, with its high sensitivity and specificity, has emerged as the gold standard in identifying and quantifying HHV-6 DNA.[4,5] Serology, cell culture and antigen detection are other techniques that may be useful in the diagnosis of HHV-6 infection.[4] As in our case of encephalitis, PCR should be performed to compare the viral load in whole blood as well as the particular body compartment when identifying an active infection in a particular body compartment.[4] Since the viral load in ciHHV-6 infected persons typically exceeds 1 million copies per mL, whole blood PCR aids in the distinction between ciHHV-6 and an infection that is actively reproducing.[5] However, studies show that for local and active CNS infections, only detectable quantities of HHV-6 DNA in the CSF are required for diagnosis regardless of the level of viral DNA in a whole blood sample.[4,6,7] Unfortunately, whole blood PCR was not performed on our patient. Contrary to CSF, an elevated viral load in plasma does not necessarily indicate an active HHV-6 infection. Increased viral DNA copies in the plasma of patients with ciHHV-6 infection may be caused by viral genome release from cellular breakdown during preliminary laboratory processing.[4-8] It is possible that viral DNA could have been preserved in the plasma due to cell lysis while undergoing either the centrifugation process or with abnormal storage temperature before processing.[9] Even with this possibility, there is incomplete, but robust, evidence against this patient having ciHHV-6 due to the increased viral load in the CSF without an accompanying rise in nucleated cell count. Compared to a ciHHV6 patient, an increased number of nucleated cells in the CSF would be expected to elevate the number of viral DNA copies.[1,9] In addition, serology showed the patient's HHV-6 IgG antibodies were undetectable at hospital admission but subsequently rose to a high level over the accompanying weeks, indicating an active infection was present. Interestingly, a prior study demonstrated a seemingly paradoxical decrease in antibody levels in individuals with ciHHV-6, not an increase. Another path to HHV-6 replication and encephalitis is the reactivation of latent infection; however, this path has its diagnostic challenges. Despite the limitations of our current knowledge of the reactivation mechanism, it appears to be triggered by discrete viral gene expression followed by an inflammatory response rather than a low level of replication, as in this instance.[4] It is unclear exactly what form the virus takes inside the cells. Although investigations have revealed that HHV-6 can reside in an episomal condition within the nucleus of some cervical cancer cell lines, there may be a consistent, low-level production or merely preservation of the genome. In addition, the viral U-94 and immediate early (IE) genes have been linked to latent infection and their expression should be visible if latency is the root of the problem.[4] However, the other elements of this case make it distinctive and reinforce our opinion that active replication of HHV-6 was the cause of our patient's condition. Genetic testing of the U94 or IE viral genes was not initiated for this patient. The report we produced has some restrictions. The absence of a whole blood PCR test is the first. Without it, we are unable to completely exclude the likelihood that this patient is a member of the 0.2%–1% of the population who are infected with ciHHV-6.[4] Taking this into account, it is probable that a hidden inflammation produced his altered mental state and was subdued throughout dexamethasone therapy. Another possibility is that despite eliminating all other apparent culprits, an undiagnosed infection nevertheless reacted to the antiviral medication. Last but not least, a latent infection may reactivate in the absence of U-94 and IE viral genetic tests. Although cautious diagnosis has been emphasised to prevent attributing encephalitis to a ciHHV-6 individual, clinical symptoms, the exclusion of other causes and treatment outcomes must also be taken into account.[10] In light of this patient's symptoms, the potential of active HHV-6 replication is increased by the clinical presentation of encephalitis with uncontrolled temporal lobe epilepsy (TLE). According to this research, astrocytes are prone to HHV-6 infection, which alters their mechanism of glutamate uptake and damages the neuronal excitatory balance seen in epilepsy.[11] According to this theory, HHV-6 could be the root cause of one-third of cases of febrile status epilepticus.[11] Furthermore, it investigates whether or not HHV-6 history is associated with TLE, a prevalent type of epilepsy. Clinically, prior neurological injury from febrile convulsions, tumours, head trauma or even infections has been linked to the refractory form of TLE. However, a recent thorough meta-analysis of the relationship between HHV-6 and refractory TLE showed that tissue from TLE-based temporal lobe resections included HHV-6 more frequently than tissue from the control group.[12] It is possible that HHV-6 was the underlying cause of our patient's seizure, especially after his car accident, given that he had a history of uncontrolled seizure activity in his left temporal lobe despite being on maintenance anti-epileptic medication and with documented exacerbation during her hospitalisation. If another bacterial, viral or fungal organism was present, it would also be expected that the number of nucleated cells in the CSF would increase.[13-15] The white blood cell count in this case was still within the normal range, which negates the presence of ciHHV-6 or any other potential causal organism. in addition, a deep delirium that coincided with the other physical and laboratory findings could not be explained by a THC toxicological assay that was positive. Furthermore, the temporal relationship between the onset of symptoms followed by a full recovery in response to treatment with ganciclovir and valganciclovir in the absence of other causative agents is far too serendipitous to be happenstance.[6] Because of these reasons, it should be deduced that a replicating HHV6 viral infection is the culprit of our patient's condition. These reported cases in Table 1 underscore the importance of early and accurate diagnosis through molecular techniques such as PCR and the potential effectiveness of antiviral treatments such as acyclovir and ganciclovir in managing HHV-6 meningoencephalitis in immunocompetent individuals.[16-18]Table 1: Case series of human herpes-6 infection in immunocompetent patientsCONCLUSION There are very few known examples, including our patient, where HHV-6 has been involved in producing encephalitis in immunocompetent people. This is because HHV-6 has frequently been proven to be the aetiology contributing to the cause of encephalitis or meningoencephalitis in immunocompromised patients. Studies have emphasised the need for caution when interpreting test findings to prevent assigning encephalitis to people who carry the ciHHV-6 virus. Undoubtedly, more research is needed to determine the clinical situation in which a patient who is immunocompetent and has encephalopathy should be examined for HHV-6 as a probable aetiology. Strong consideration for the use of antiviral therapy should be offered in those individuals determined to have a confirmed diagnosis of HHV-6 encephalitis as an essential component of treatment management. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest. 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