Chandipura Virus

Introduction

Classification

• Family: Rhabdoviridae (from Greek rhabdos = rod, referring to the bullet/rod shape of virions)
• Genus: Vesiculovirus (the same genus as vesicular stomatitis virus). The other medically important genus in this family is Lyssavirus (rabies and rabies-like viruses) - Jawetz, Melnick & Adelberg's Medical Microbiology, 28E; Medical Microbiology, 9E.
• CHPV is grouped among the arboviruses prevalent in India under "Others," alongside Chittoor, Ganjam, Minnal, Dhori, and Kaisodi viruses - Park's Textbook of Preventive and Social Medicine.

Structure

• Bullet- or rod-shaped, enveloped virion, roughly 50-95 nm in diameter and 130-380 nm in length.
• Envelope studded with glycoprotein (G) spikes/peplomers that mediate attachment and induce neutralizing antibodies.
• Genome: single-stranded, negative-sense RNA (~11-12 kb) enclosed in a helical nucleocapsid giving a striated appearance.
• Structural proteins: nucleoprotein (N, protects RNA and maintains transcription-competent conformation), large (L) and phosphoprotein/NS (together forming the RNA-dependent RNA polymerase), and matrix (M) protein between the envelope and nucleocapsid (Medical Microbiology, 9E).

Epidemiology and Transmission

• Vectors: Sandflies (Phlebotomus and Sergentomyia species) are the principal vectors; mosquitoes (Aedes aegypti) have also been implicated (Harrison's, 22E).
• Reservoir: Hedgehogs have been proposed as an amplifying/reservoir host, with the virus also detected in hedgehogs and sandflies in Nigeria and Senegal, though human disease outside India is not well documented.
• Geography: Endemic to central, western, and southern India - Gujarat, Maharashtra, Andhra Pradesh, Madhya Pradesh, Karnataka, Tamil Nadu, Odisha, Bihar, and Rajasthan. Gujarat experiences recurrent outbreaks roughly every 4-5 years, typically during the monsoon season.
• Age group: Predominantly affects children under 15 years.
• A major outbreak in Andhra Pradesh in 2003 caused a high-fatality acute encephalitis illness in children and drew international attention to CHPV (cited in Bradley and Daroff's Neurology in Clinical Practice, referencing Rao et al., Lancet 2004).
• Most recently, a large outbreak occurred in Gujarat and Rajasthan in 2024: the WHO reported 245 acute encephalitis syndrome (AES) cases between June and August 2024, with 82 deaths (CFR ~33%); 64 cases were laboratory-confirmed for CHPV.

Pathogenesis

Clinical Features

• Abrupt onset of an influenza-like prodrome: high-grade fever, headache, myalgia, abdominal pain, nausea and vomiting.
• Rapid progression (often within 24-48 hours) to altered sensorium, seizures, and signs of encephalitis.
• The illness can progress fulminantly to coma and death within a day or two of hospital presentation, explaining the very high case fatality rate.
• Survivors generally have relatively mild EEG changes and recover with few neurologic sequelae, in contrast to the high mortality seen in fatal cases.
• Other arthropod-borne rhabdoviruses (Isfahan, Piry, vesicular stomatitis Indiana and New Jersey viruses) can mimic the early febrile phase of CHPV infection.

Diagnosis

• Clinical suspicion in a child from an endemic region presenting with rapid febrile encephalopathy during monsoon season.
• Laboratory confirmation: IgM ELISA and RT-PCR on serum/CSF (as used in the 2024 Gujarat outbreak investigation by ICMR-NIV Pune).
• Virus isolation is difficult since CSF is frequently negative even in confirmed cases; diagnosis often relies on serology and molecular testing on serum.

Treatment and Prevention

• No specific antiviral therapy or licensed vaccine exists; management is purely supportive - control of fever, seizures, raised intracranial pressure, and general intensive care.
• Prevention centers on vector control (insecticide spraying against sandflies/mosquitoes, use of repellents and bed nets), community health education, and active AES surveillance to allow early case detection and outbreak response, as coordinated through India's Hospital-based Acute Encephalitis Syndrome Surveillance Network.

Recent Literature Note

Encephalitis & Encephalopathy

1. Definitions (2 marks)

• Encephalitis: Inflammation of the brain parenchyma, secondary to infection (most often viral) or an inflammatory/immune response, almost invariably associated with meningeal inflammation (meningoencephalitis) - Robbins & Kumar Basic Pathology; The Harriet Lane Handbook.
• Encephalopathy: A state of diffuse neuronal dysfunction manifesting as acute or chronic altered mental status, without necessarily implying inflammation - it may be caused by metabolic, toxic, hypoxic, or infectious insults that impair global brain function - The Harriet Lane Handbook; Plum and Posner's Diagnosis and Treatment of Stupor and Coma.

2. Viral Etiological Agents of Encephalitis/Encephalopathy (3 marks)

• Herpes simplex virus (HSV-1, HSV-2) - most common cause of sporadic fatal encephalitis
• Varicella-zoster virus (VZV)
• Epstein-Barr virus (EBV)
• Cytomegalovirus (CMV, especially in immunocompromised/congenital infection)
• Human herpesvirus 6 (HHV-6)

• Japanese encephalitis virus (Flavivirus) - most important in India/Asia
• West Nile virus (Flavivirus)
• Eastern/Western equine encephalitis virus (Togavirus)
• Chandipura virus (Rhabdoviridae, genus Vesiculovirus) - sandfly/mosquito-borne, important emerging cause in India
• La Crosse and other California encephalitis group viruses (Bunyaviridae)

• Poliovirus, Coxsackievirus, Echovirus, Enterovirus 71

• Rabies virus (Lyssavirus, Rhabdoviridae)
• Measles virus (acute encephalitis, postinfectious encephalomyelitis, SSPE)
• Mumps virus
• Nipah virus
• Rubella virus (congenital)

• HIV (HIV encephalopathy/AIDS dementia complex)

3. Detailed Account: Herpes Simplex Encephalitis (7 marks)

• Acute onset of fever, headache, and altered consciousness
• Focal features reflecting temporal lobe involvement: behavioral/personality changes, aphasia, memory disturbance, other focal neurologic deficits
• Seizures are common (both focal and generalized)
• Rapid progression to stupor/coma if untreated, with risk of temporal lobe swelling and herniation

• CSF analysis: lymphocytic pleocytosis (25-75 WBC/µL, 75-90% mononuclear cells), mildly elevated protein (65-85 mg/dL), normal glucose
• MRI (more sensitive than CT): unilateral temporal lobe hyperintensity/edema in early disease, which may become bilateral
• EEG: may show periodic lateralized epileptiform discharges (PLEDs) over the temporal lobe
• Confirmatory test: detection of HSV DNA by PCR in CSF - the gold standard

• Intravenous acyclovir, 10 mg/kg every 8 hours for 14-21 days, should be started empirically in any patient with suspected viral encephalitis (especially with focal features) while awaiting confirmatory tests, because acyclovir acts by viral thymidine kinase-mediated phosphorylation to a triphosphate that inhibits viral DNA polymerase, with minimal toxicity to uninfected cells.
• Without treatment: mortality exceeds 70%, with fewer than 10% of survivors returning to baseline function.
• With early acyclovir therapy: mortality falls to 10-25%, and 40-55% of patients can resume normal activities of daily living.
• Long-term oral valacyclovir after IV acyclovir provides no added benefit. Relapsing symptoms after treatment are increasingly recognized as a postinfectious autoimmune phenomenon, particularly anti-NMDA receptor encephalitis, rather than true viral relapse.