High seroprevalence of human herpesviruses in HIV-infected individuals attending primary healthcare facilities in rural South Africa

Seroprevalence data of human herpesviruses (HHVs) are limited for sub-Saharan Africa. These are important to provide an indication of potential burden of HHV-related disease, in particular in human immunodeficiency virus (HIV)-infected individuals who are known to be at increased risk of these conditions in the Western world. In this cross-sectional study among 405 HIV-infected and antiretroviral therapy naïve individuals in rural South Africa the seroprevalence of HHVs was: herpes simplex virus type 1 (HSV-1) (98%), herpes simplex virus type 2 (HSV-2) (87%), varicella zoster virus (VZV) (89%), and 100% for both Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Independent factors associated with VZV seropositivity were low educational status and having children. Lack of in-house access to drinking water was independently associated with positive HSV-1 serostatus, whereas Shangaan ethnicity was associated with HSV-2 seropositivity. Increasing age was associated with higher IgG titres to both EBV and CMV, whereas CD4 cell count was negatively associated with EBV and CMV IgG titres. Moreover, IgG titres of HSV-1 and 2, VZV and CMV, and CMV and EBV were positively correlated. The high HHV seroprevalence emphasises the importance of awareness of these viral infections in HIV-infected individuals in South Africa

High seroprevalence of human herpesviruses in HIV-infected individuals attending primary healthcare facilities in rural South Africa

Seroprevalence data of human herpesviruses (HHVs) are limited for sub-Saharan Africa. These are important to provide an indication of potential burden of HHV-related disease, in particular in human immunodeficiency virus (HIV)-infected individuals who are known to be at increased risk of these conditions in the Western world. In this cross-sectional study among 405 HIV-infected and antiretroviral therapy naïve individuals in rural South Africa the seroprevalence of HHVs was: herpes simplex virus type 1 (HSV-1) (98%), herpes simplex virus type 2 (HSV-2) (87%), varicella zoster virus (VZV) (89%), and 100% for both Epstein-Barr virus (EBV) and cytomegalovirus (CMV). Independent factors associated with VZV seropositivity were low educational status and having children. Lack of in-house access to drinking water was independently associated with positive HSV-1 serostatus, whereas Shangaan ethnicity was associated with HSV-2 seropositivity. Increasing age was associated with higher IgG titres to both EBV and CMV, whereas CD4 cell count was negatively associated with EBV and CMV IgG titres. Moreover, IgG titres of HSV-1 and 2, VZV and CMV, and CMV and EBV were positively correlated. The high HHV seroprevalence emphasises the importance of awareness of these viral infections in HIV-infected individuals in South Africa

Clinical and corneal microbial profile of infectious keratitis in a high HIV prevalence setting in rural South Africa

The purpose of this investigation was to determine the clinical and corneal microbial profile of infectious keratitis in a high human immunodeficiency virus (HIV) prevalence setting in rural South Africa. Data in this cross-sectional study were collected from patients presenting with symptoms of infectious keratitis (n = 46) at the ophthalmology outpatient department of three hospitals in rural South Africa. Corneal swabs were tested for herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), varicella zoster virus (VZV) and adenovirus DNA by real-time polymerase chain reaction (PCR

Central nervous system disease and genital disease in harbor porpoises (Phocoena phocoena) are associated with different herpesviruses

Herpesvirus infection causes disease of variable severity in many species, including cetaceans. However, little is known about herpesvirus infection in harbor porpoises (Phocoena phocoena), despite being widespread in temperate coastal waters of the Northern Hemisphere. Therefore, we examined harbor porpoises that stranded alive in the Netherlands, Belgium, and Germany between 2000 and 2014 for herpesvirus infection and associated disease. Porpoises that died or had to be euthanized were autopsied, and samples were collected for virological and pathological analyses. We found one known herpesvirus (Phocoena phocoena herpesvirus type 1, PPHV-1) - a gammaherpesvirus - and two novel herpesviruses (PPHV-2 and PPHV-3) - both alphaherpesviruses - in these porpoises. A genital plaque, in which PPHV-1 was detected, occurred in 1% (1/117) of porpoises. The plaque was characterized by epithelial hyperplasia and intranuclear inclusion bodies that contained herpesvirus-like particles, and that stained positive by a PPHV-1-specific in situ hybridization test. PPHV-2 occurred in the brain of 2% (1/74) of porpoises. This infection was associated with lymphocytic encephalitis, characterized by neuronal necrosis and intranuclear inclusion bodies containing herpesvirus-like particles. PPHV-3 had a prevalence of 5% (4/74) in brain tissue, 5% (2/43) in blowhole swabs, and 2% (1/43) in genital swabs, but was not associated with disease. Phylogenetically, PPHV-1 was identical to a previously reported herpesvirus from a harbor porpoise, PPHV-2 showed closest identity with two herpesviruses from dolphins, and PPHV-3 showed closest identity with a cervid herpesvirus. In conclusion, harbor

T-Cell Tropism of Simian Varicella Virus during Primary Infection

Varicella-zoster virus (VZV) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. The cell types that transport VZV from the respiratory tract to skin and ganglia during primary infection are unknown. Clinical, pathological, virological and immunological features of simian varicella virus (SVV) infection of non-human primates parallel those of primary VZV infection in humans. To identify the host cell types involved in virus dissemination and pathology, we infected African green monkeys intratracheally with recombinant SVV expressing enhanced green fluorescent protein (SVV-EGFP) and with wild-type SVV (SVV-wt) as a control. The SVV-infected cell types and virus kinetics were determined by flow cytometry and immunohistochemistry, and virus culture and SVV-specific real-time PCR, respectively. All monkeys developed fever and skin rash. Except for pneumonitis, pathology produced by SVV-EGFP was less compared to SVV-wt. In lungs, SVV infected alveolar myeloid cells and T-cells. During viremia the virus preferentially infected memory T-cells, initially central memory T-cells and subsequently effector memory T-cells. In early non-vesicular stages of varicella, SVV was seen mainly in perivascular skin infiltrates composed of macrophages, dendritic cells, dendrocytes and memory T-cells, implicating hematogenous spread. In ganglia, S

Detection of circovirus in Foxes with Meningoencephalitis, United Kingdom, 2009–2013

A fox circovirus was identified in serum samples from foxes with unexplained neurologic signs by using viral metagenomics. Fox circovirus nucleic acid was localized in histological lesions of the cerebrum by in situ hybridization. Viruses from the family Circoviridae may have neurologic tropism more commonly than previously anticipated

Norovirus infection in harbor porpoises

A norovirus was detected in harbor porpoises, a previously unknown host for norovirus. This norovirus had low similarity to any known norovirus. Viral RNA was detected primarily in intestinal tissue, and specific serum antibodies were detected in 8 (24%) of 34 harbor porpoises from the North Sea

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension

Functional Characterization of Ocular-Derived Human Alphaherpesvirus Cross-Reactive CD4 T Cells

Intraocular varicella-zoster virus (VZV) and HSV type 1 (HSV-1) infections cause sight-threatening uveitis. The disease is characterized by an intraocular inflammatory response involving herpesvirus-specific T cells. T cell reactivity to the noncausative human alphaherpesvirus (alpha HHV) is commonly detected in the affected eyes of herpetic uveitis patients, suggesting the role of cross-reactive T cells in the disease. This study aimed to identify and functionally characterize intraocular human alphaherpesvirus cross-reactive T cells. VZV protein immediate early 62 (IE62), which shares extensive homology with HSV ICP4, is a previously identified T cell target in VZV uveitis. Two VZV-specific CD4 T cell clones (TCC), recovered from the eye of a VZV uveitis patient, recognized the same IE62(918-927) peptide using different TCR and HLA-DR alleles. The IE62(918-927) peptide bound with high affinity to multiple HLA-DR alleles and was recognized by blood-derived T cells of 5 of 17 HSV-1/VZV-seropositive healthy adults but not in cord blood donors (n = 5). Despite complete conservation of the IE62 epitope in the orthologous protein ICP4 of HSV-1 and HSV-2, the TCC recognized VZV and HSV-1-but not HSV-2-infected B cells. This was not attributed to proximal epitope-flanking amino acid polymorphisms in HSV-2 ICP4. Notably, VZV/ HSV-1 cross-reactive CD4 T cells controlled VZV but not HSV-1 infection of human primary retinal pigment epithelium (RPE) cells. In conclusion, we report on the first VZV/ HSV-1 cross-reactive CD4 T cell epitope, which is HLA-DR promiscuous and immunoprevalent in coinfected individuals. Moreover, ocular-derived peptide-specific CD4 TCC controlled VZV but not HSV-1 infection of RPE cells, suggesting that HSV-1 actively inhibits CD4 T cell activation by infected human RPE cells