Association of Neurotropic Viruses in HIV-Infected Individuals Who Died of Secondary Complications of Tuberculosis, Cryptococcosis, or Toxoplasmosis in South India

Abstract

The frequencies of 10 opportunistic DNA viruses were determined by multiplex real-time PCR in paired cerebrospinal fluid (CSF) and brain tissue of HIV-infected individuals. In the CSF, viruses were detectable in 45/55 cases: JC virus (JCV) in 62%, Epstein-Barr virus (EBV) in 44%, cytomegalovirus (CMV) in 25%, varicella-zoster virus (VZV) in 3.6%, herpes simplex virus 1 (HSV-1) in 1.8%, and human herpesvirus 6 (HHV-6) in 1.8% of cases. A single virus was detectable in 20 cases, 19 cases had coinfection with two viruses, and 6 cases were positive for three viruses. JCV was detectable in the CSF of 62% of cases and in 42% of brain tissues, with higher loads in progressive multifocal leukoencephalopathy (PML) (P < 0.05). Several viruses can cause opportunistic infections in HIV-infected individuals, with high morbidity and mortality in HIVinfected individuals (1). These infections are more frequently reactivation of the latent viruses in the host. It is essential to identify the causative agent of these opportunistic infections to initiate therapy or prophylactic treatment. As the clinical pictures caused by different viruses often overlap and multiple infections are also frequent in immunocompromised hosts, simultaneous screening of a wide range of viruses would be cost-effective management (2). Viruses like Epstein-Barr virus (EBV), cytomegalovirus (CMV), and JC virus (JCV) can result in life-threatening infections in the central nervous system (CNS) of immunodeficient individuals (3, 4). The clinical conditions include primary CNS lymphoma, cytomegalovirus encephalitis, and progressive multifocal leukoencephalopathy (PML) (5-7). To compound the clinical problem, viral infections can coexist with bacterial and fungal infections. Currently, there are no reports from India on the frequency of CNS viral infections among HIV-1-infected individuals. The aim of this study was to develop a real-time multiplex PCR for the simultaneous detection of DNA viruses in paired CSF and brain tissue samples of HIV-infected individuals.The study was carried out in the Departments of Clinical Virology (site 1) and Neuropathology (site 2) of two tertiary care centers in south India. The study was approved by the institutional review boards of both institutions. Brain tissues and CSF samples of histopathologically well-characterized HIV-associated opportunistic infections collected at autopsy and archived in the Human Brain Tissue Repository of Neuropathology were utilized for the study. All the samples archived were collected at autopsy following written informed consent from the legal close relative(s) of the deceased to use the biological material for research.A total of 55 archived paired CSF and brain tissue samples collected from HIV-positive individuals who had died with confirmed bacterial or fungal infections were investigated. These diagnoses were confirmed by histopathology, immunohistochemistry, and/or microbiological methods (culture, serology). The study also included 20 CSF samples collected from patients who died of non...

Significance of Epstein-Barr virus (HHV-4) and CMV (HHV-5) infection among subtype-C human immunodeficiency virus-infected individuals

“…A study form our center reported JCV DNA in the CSF (62% of samples) and brain tissue samples (42% of the samples tested) from HIV-infected individuals. [21] One notable finding in our study is that all the 291 tested samples were also found negative for HHV-8 DNA. [25] There was a significant association with elevated SGPT/ SGOT serum level with high EBV and CMV loads.…”

“…In case of CMV 8 (89%) samples were genotype gB1 and 1 (11%) sample showed genotype gB2 in organ-specific samples like CSF and brain tissue samples. [21] Currently there are no reports on EBV genotypes among HIV-infected individuals from India other than our study. A recent study reported from New Delhi, India had studied the glycoprotein B genotypes in blood and urine of babies with symptomatic congenital/perinatal CMV infection and found gB 1, 2 and 3 genotypes in the population.…”

“…The lower detection limits for all the viruses were previously reported [21] except for adenovirus the lower detection of limit was 15 plasmids/10 µl input (1500 copies/ml).…”

Progressive Multifocal Leukoencephalopathy Associated with Pulmonary Tuberculosis in an Immuno-Compromised Indian Patient

“…As per the previous records death usually occurs within 9 to 12 months in 80% of the cases but again it depends on the time of initiation of ART and the viral load [24,25]. A previous study determined JCV DNA loads in patients with HIV and tuberculosis but did not present MRI findings [26]. This case report is of special interest because it uses both PCR and MRI to diagnose PML in a HIV positive patient with tuberculosis.…”

Reactivation of Multiple Infectious Pathogens after Hematopoietic Stem Cell Transplantation

“…Toxoplasma encephalitis is 1 of 3 leading focal central nervous system complications in patients with AIDS. The association of JCV and toxoplasma was reported when 41% of the HIV-infected patients had detectable JCV in CSF [8]. However, in another study performed in 331 HIV-infected adults in Zambia, none of the JCV-positive CSF had toxoplasmosis detected [9].…”