Cytomegalovirus Reactivation Following Streptococcus Meningitis
Year: 2026
Type: article
Study design: Case Report
Abstract: Sir, Patient 1: A 32-year-old female with systemic lupus erythematosus (SLE) presented with headache and fever and was diagnosed with Streptococcus pneumoniae meningitis via cerebrospinal fluid (CSF) culture and metagenomic next-generation sequencing (mNGS) [Figure 1a]. After treatment with meropenem, her symptoms initially improved, but a recurrence of fever, fatigue, and cognitive decline occurred after 11 days. Linezolid was added but failed to produce improvement, necessitating her transfer to our institution. A repeat mNGS revealed residual Streptococcus pneumoniae and 4716 reads of cytomegalovirus (CMV)-specific sequences [Figure 1b], confirmed by RT-PCR with 1920 copies/ml. Treatment with ganciclovir led to significant recovery, with no symptoms reported during a 2-month follow-up.Figure 1: Analysis of sequencing results of Streptococcus and cytomegalovirus (CMV). (a) Patient 1 cerebrospinal fluid (CSF) metagenomic next-generation sequencing (mNGS) coverages mapped to Streptococcus pneumoniae. (b) Patient 1 CSF mNGS coverages mapped to cytomegalovirus. (c) Patient 2 CSF mNGS coverages mapped to Streptococcus suis. (d) Patient 2 CSF mNGS coverages mapped to cytomegalovirusPatient 2: A 58-year-old male with no significant medical history was admitted to a local hospital with fever and headache. CSF culture later confirmed Streptococcus suis meningitis. Despite initial improvement on ceftriaxone and linezolid, he developed severe hearing impairment and was transferred to our hospital. mNGS revealed six specific sequences of Streptococcus suis [Figure 1c]. His symptoms, excluding hearing impairment, improved after continuing linezolid, and he was discharged on oral linezolid. He experienced a recurrence of headaches 7 days after discharge, followed shortly by recurrent tonic convulsions and loss of consciousness. Magnetic resonance imaging (MRI) indicated meningoencephalitis [Figure 2a]. The mNGS test detected a high burden of CMV sequences [Figure 1d] but no Streptococcus suis sequences in the CSF. Ganciclovir treatment resulted in symptom relief and the disappearance of abnormal signals on MRI [Figure 2b]. Except for hearing impairment, no symptoms were reported during the 2-month follow-up.Figure 2: T2-weighted magnetic resonance image (T2WI) fluid-attenuated inversion recovery (FLAIR) images of patient 2. (a) T2WI FLAIR images showed multiple abnormal signals in the meninges, extending to the subjacent frontal lobe cortex. (b) The T2WI FLAIR hyperintensities almost completely disappeared following treatmentTable 1 shows the sequential timeline of CSF analysis and the results of pathogen examinations and the corresponding treatments. Figure 3 illustrates the changes in CSF analysis and symptoms over time, along with the primary medications.Table 1: Results of lumbar puncture and cerebrospinal fluid analysis in patients with clinical notesFigure 3: Timeline of cerebrospinal fluid (CSF) assessments and primary treatments for the cases studied. For both patient 1 (a) and patient 2 (b), CSF assessments include opening pressure and white blood cell count on the left axis, with protein and glucose levels on the right axisThese cases highlight the unexpected reactivation of CMV following streptococcus meningitis, a phenomenon that has not been previously documented. When a diagnosis of Streptococcus meningitis is confirmed and effective antibacterial treatment has been initiated, if the patient experiences a recurrence of symptoms that cannot be explained by other causes after an initial improvement, it is important to consider the possibility of other unusual occurrences, such as CMV reactivation as mentioned in this case report. Imaging studies, such as MRI, that reveal brain parenchymal lesions distinct from those typically associated with meningitis can provide crucial evidence to guide further differential diagnosis. Bacterial infections might reactivate latent viruses through several mechanisms. First, severe bacterial infections can suppress both innate and adaptive immune responses, potentially reducing the threshold for viral reactivation.[1,2] Second, cytokines such as IL-6 and TNF-α are upregulated in response to bacterial infections in the meninges and are known to play roles in the activation of latent viruses, including CMV.[3,4] Third, the physiological stress from bacterial infections can induce DNA damage and oxidative stress, which in turn might activate viral promoters, leading to CMV replication.[5] The mNGS technology is a powerful tool for diagnosing infectious diseases, particularly in complex clinical scenarios.[6] It can detect a wide range of pathogens without prior knowledge of the causative agent. However, it also carries the potential for false positives and presents challenges in accurately identifying pathogenic organisms. In conclusion, our report underscores the complexity of CNS infections and the critical need for advanced diagnostic tools such as mNGS. Understanding the interplay between bacterial infections and viral reactivation is essential for improving patient outcomes. 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.
Source: Neurology India
Authors: Xiaofeng Xu, Ting Fang, Ying Jiang, Fuhua Peng
Language: English
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W7119514696