Herpes Simplex Virus Infection Research Articles

Associations of attention-deficit/hyperactivity disorder with inflammatory diseases. Results from the nationwide German Health Interview and Examination Survey for Children and Adolescents (KiGGS).

Despite conflicting data, some studies have suggested apathophysiological relationship between inflammation and attention-deficit/hyperactivity disorder (ADHD). Using data from the nationwide and representative German Health Interview and Examination Survey for Children and Adolescents (KiGGS; n = 6922 study participants aged 11-17years), this posthoc analysis assessed the associations between ADHD and three common inflammatory diseases. Results showed univariate associations between ADHD and lifetime inflammatory diseases including atopic dermatitis (p = 0.002), otitis media (p = 0.001), and herpes simplex infection (p = 0.032). In logistic regression models adjusted for clinically relevant confounders, we found that ADHD remained asignificant predictor of all three inflammatory diseases (atopic dermatitis, Exp(β) = 1.672, 95% confidence interval [CI] 1.239-2.257, p = 0.001; otitis media, Exp(β) = 1.571, 95% CI 1.209-2.040, p = 0.001; herpes simplex, Exp(β) = 1.483, 95% CI 1.137-1.933, p = 0.004). Our findings demonstrate apositive link between ADHD and peripheral inflammatory diseases, including atopic dermatitis, otitis media, and herpes simplex infection. Further studies are needed to understand the exact pathophysiological mechanisms underlying these associations.

Causal associations between prodromal infection and neuromyelitis optica spectrum disorder: A Mendelian randomization study.

Prodromal infections are associated with neuromyelitis optica spectrum disorder (NMOSD), but it remains unclear which type of infection has a causal association with NMOSD. We aimed to explore the causal associations between four herpesvirus infections (chickenpox, cold sores, mononucleosis and shingles) and NMOSD, as well as between other types of infections and NMOSD. For data on infections, we used the genome-wide association study (GWAS) summary statistics from the 23andMe cohort. For outcomes, we used the GWAS data of participants of European ancestry, including 215 NMOSD patients (132 anti-aquaporin-4 antibody [AQP4-ab]-positive patients and 83 AQP4-ab-negative patients) and 1244 normal controls. Single-nucleotide polymorphism (SNP) identification and two-sample Mendelian randomization (MR) analyses were then performed. In the 23andMe cohort, we identified one SNP for chickenpox (rs9266089 in HLA-B gene), one SNP for cold scores (rs885950 in the POU5F1 gene), one SNP for mononucleosis (rs2596465 in the HCP5 gene), and three SNPs for shingles (rs2523591 in the HLA-B gene; rs7047299 in the IFNA21 gene; rs9260809 in the MICD gene). The association between cold sores and AQP4-ab-positive NMOSD reached statistical significance (odds ratio [OR] 745.318; 95% confidence interval [CI] 22.176, 25,049.53 [p < 0.001, Q < 0.001]). The association between shingles and AQP4-ab-positive NMOSD was also statistically significant (OR 21.073; 95% CI 4.271, 103.974 [p < 0.001, Q < 0.001]). No significant association was observed between other infections and AQP4-ab-positive or AQP4-ab-negative NMOSD. These findings suggest there are positive associations between cold sores and shingles and AQP4-ab-positive NMOSD, indicating there may be causal links between herpes simplex virus and varicella-zoster virus infection and AQP4-ab-positive NMOSD.

Rare Presentation of Immune Compromised District: Disseminated Herpes Simplex Infection over Active Dermatophytosis in an Immunocompromised Patient

Immunocompromised districts are the localised areas of immune deficiency in skin. It is more vulnerable than the rest of the body for infections or other dermatoses. The factors responsible for localised immune dysregulation can be multifarious such as herpetic infections, burns, trauma, ionising or ultraviolet radiations and chronic lymphatic stasis. Herpes simplex virus belongs to the herpesviridae family and can cause mucocutaneous as well as genital skin lesions. Here, we report a rare presentation of disseminated herpes simplex infection over the dermatophytosis skin lesions in a tuberculosis patient with chronic kidney disease.

Herpetic Esophagitis Mimicking Carcinoma In Situ

Herpes Simplex virus (HSV) type I is a common infectious agent of nongenital areas and has been diagnosed most frequently in esophagitis even in otherwise healthy subjects. Although some mild cellular alterations are commonly seen in this disease they can hardly be so intense as to simulate a carcinoma in situ of squamous epithelium. We report such a case and call attention to the possibility of an overdiagnosis of cancer. Some observations in literature relating HSV infection. to cancer are also made.

NLRC4 promotes the cGAS-STING signaling pathway by facilitating CBL-mediated K63-linked polyubiquitination of TBK1.

TANK-binding kinase 1 (TBK1) is crucial in producing type Ⅰ interferons (IFN-Ⅰ) that play critical functions in antiviral innate immunity. The tight regulation of TBK1, especially its activation, is very important. Here we identify NLRC4 as a positive regulator of TBK1. Ectopic expression of NLRC4 facilitates the activation of the IFN-β promoter, the mRNA levels of IFN-β, ISG54, and ISG56, and the nuclear translocation of interferon regulatory factor 3 induced by cGAS and STING. Consistently, under herpes simplex virus-1 (HSV-1) infection, knockdown or knockout of NLRC4 in BJ cells and primary peritoneal macrophages from Nlrc4-deficient (Nlrc4-/- ) mice show attenuated Ifn-β, Isg54, and Isg56 mRNA transcription, TBK1 phosphorylation, and augmented viral replications. Moreover, Nlrc4-/- mice show higher mortality upon HSV-1 infection. Mechanistically, NLRC4 facilitates the interaction between TBK1 and the E3 ubiquitin ligase CBL to enhance the K63-linked polyubiquitination of TBK1. Our study elucidates a previously uncharacterized function for NLRC4 in upregulating the cGAS-STING signaling pathway and antiviral innate immunity.

Neonatal herpes simplex virus infection: From the maternal infection to the child outcome.

This review examines the recent literature on the management of herpes simplex virus (HSV) infections in neonates. We summarized the three clinical categories of maternal HSV infection during pregnancy (primary first episode, nonprimary first episode, or recurrent episode) and the mechanisms of fetal damage. Considering when the transmission of the infection from the mother to the fetus/newborn occurs, three types of neonatal infection can be distinguished: intrauterine infection (5% of cases), postnatal infection (10% of cases), and perinatal infections (85% of cases). Neonatal presentation could range from a limited disease with skin, eye, and mouth disease to central nervous system disease or disseminated disease: the treatment with acyclovir should be tailored according to symptoms and signs of infection, and virological tests. These children need a multidisciplinary follow-up, to timely intercept any deviation from normal neurodevelopmental milestones. Prevention strategies remain a challenge, in the absence of an available vaccine against HSV.

PANoptosome signaling and therapeutic implications in infection: central role for ZBP1 to activate the inflammasome and PANoptosis.

The innate immune response provides the first line of defense against infection and disease. Regulated cell death (RCD) is a key component of innate immune activation, and RCD must be tightly controlled to clear pathogens while preventing excess inflammation. Recent studies have highlighted a central role for the innate immune sensor Z-DNA-binding protein 1 (ZBP1) as an activator of a form of inflammatory RCD called PANoptosis, which is regulated by a multifaceted cell death complex called the PANoptosome. In response to influenza A virus infection, ZBP1 activates the nucleotide-bindingoligomerizationdomain-like receptor family pyrin domain-containing protein 3(NLRP3) inflammasome, which then acts as an integral component of the ZBP1-PANoptosome to drive inflammatory cell death, PANoptosis. In this context, the NLRP3 inflammasome is critical for caspase-1 activation and proinflammatory cytokine interleukin (IL)-1β and IL-18 maturation, but dispensable for cell death due to functional redundancies between PANoptosome molecules. Similarly, ZBP1 is also central to the absent in melanoma 2 (AIM2)-PANoptosome; this PANoptosome forms in response to Francisella novicida and herpes simplex virus 1infection and incorporates the AIM2 inflammasome as an integral component. In this review, we will discuss the critical roles of ZBP1 in mediating innate immune responses through inflammasomes, PANoptosomes, and PANoptosis during infection. An improved understanding of the molecular mechanisms of innate immunity and cell death will be essential for the development of targeted modalities that can improve patient outcomes by mitigating severe disease.

Characteristics of neonatal herpes simplex central nervous system disease in Australia (1997-2020).

Neonatal herpes simplex virus (HSV) central nervous system (CNS) disease can occur in isolation or as part of disseminated infection. We sought to describe neonatal HSV CNS disease in Australia over 24 years. Neonates (≤28 days) with confirmed HSV infection, reported prospectively to the Australian Paediatric Surveillance Unit (1997-2020), were evaluated for HSV CNS disease (laboratory confirmation with clinical evidence of encephalitis, e.g., lethargy, seizures, focal signs; and/or abnormalities on neuroimaging or electroencephalogram), and compared with neonates without CNS disease. CNS-restricted disease was compared with CNS-disseminated disease. Of 195 neonates with HSV disease; 87 (45%) had CNS disease (1.29 cases/100,000 live births per year, 95% CI: 1·04-1·59). Neonates with CNS disease were significantly more likely to be male than neonates without CNS disease (60% versus 39%, OR=2·32, 95% CI 1·29-4·18). Of the neonates with CNS disease, those with CNS-restricted disease (52/87, 60%) presented later than neonates with CNS-disseminated disease (35/87, 40%), (mean 12 versus 6 days). Twenty (23%) neonates with CNS disease died, the majority with CNS-disseminated disease (n=19). Most neonates received aciclovir therapy (94·3%), however five neonates with unrecognised CNS disseminated disease (diagnosed at autopsy) had not been treated. Survivors of CNS disease were significantly more likely to have adverse neurological sequelae, compared with those without CNS disease (30% versus 4%, OR: 9·60, 95% CI: 2·6-35·0). Male neonates have a higher burden of HSV CNS disease. Despite the use of antiviral agents, morbidity following neonatal HSV CNS disease remains high. Evaluation of adjunctive therapies to improve outcomes is needed.

The HSV-1 ICP22 protein selectively impairs histone repositioning upon Pol II transcription downstream of genes

Herpes simplex virus 1 (HSV-1) infection and stress responses disrupt transcription termination by RNA Polymerase II (Pol II). In HSV-1 infection, but not upon salt or heat stress, this is accompanied by a dramatic increase in chromatin accessibility downstream of genes. Here, we show that the HSV-1 immediate-early protein ICP22 is both necessary and sufficient to induce downstream open chromatin regions (dOCRs) when transcription termination is disrupted by the viral ICP27 protein. This is accompanied by a marked ICP22-dependent loss of histones downstream of affected genes consistent with impaired histone repositioning in the wake of Pol II. Efficient knock-down of the ICP22-interacting histone chaperone FACT is not sufficient to induce dOCRs in ΔICP22 infection but increases dOCR induction in wild-type HSV-1 infection. Interestingly, this is accompanied by a marked increase in chromatin accessibility within gene bodies. We propose a model in which allosteric changes in Pol II composition downstream of genes and ICP22-mediated interference with FACT activity explain the differential impairment of histone repositioning downstream of genes in the wake of Pol II in HSV-1 infection.

Monkeypox Infection, what we need to Know About

Monkeypox virus is an orthopoxvirus which was isolated for the first time in the 1950s from a group of unwell monkeys. It is in the same genus as variola that causes smallpox and vaccinia viruses. Although they are famously suspicious, there’s no clear evidence that monkeys are the primary natural reservoir of the Monkeypox virus. However, humans and monkeys are considered to be incidental hosts. Monkeypox is usually acquired by humans through contact with animal fluid or bites, nevertheless, the human-to-human infection may occur through contact with infectious skin, exposure to large respiratory droplets and/or prolonged face-to-face contact within 6 feet for more than 3 hours without appropriate protections. Interestingly, the most recent outbreak that took place in May 2022 in non-endemic places has been linked to some sexual activities through an unknown mechanism. After the discontinuation of smallpox vaccination in 1979, monkeypox was endemic in Central and West Africa with sporadic cases reported in other non-endemic countries, mostly in returning travellers from endemic areas. In 2003, the United States of America reported an outbreak of monkeypox virus from infected prairie dogs who were in contact with imported animals from Africa. The incubation period of the monkeypox virus is 6 to 13 days with a range of 5 to 21 days. The most common presenting features of monkeypox are rash, fever, lymphadenopathy, chills, and myalgias. It is usually a mild disease that might be associated with nausea and vomiting, and Most of the infected persons recover without intervention. However, more serious cases might require hospitalization and supportive care. Laboratory confirmatory tests are essential to differentiate monkeypox from fever and rash diseases. These include (i) virus isolation in mammalian cell cultures, (ii) direct electron microscopy, (iii) real-time polymerase chain reaction (PCR), and (iv) enzyme-linked immunosorbent assay (ELISA), and (v) immunofluorescent antibody assay. The public health authorities should be notified according to most states’ health regulations. Varicella, smallpox, herpes simplex infection, and other orthopoxvirus infections are the differential diagnosis for Monkeypox. Tecovirimat and brincidofovir are the approved antiviral treatment for smallpox in the United States as their activity against monkeypox are approved in animals and are expected to be effective in human infection. Cidofovir has in vitro effect against monkeypox with a particular effect against lethal monkeypox in animal models. Contact, droplet, and airborne standard precaution measures are essential for any hospitalized patient with a generalized unknown vesicular rash as monkeypox and smallpox are part of the differential diagnosis. Pre- and post-exposure smallpox vaccination prophylaxis are reasonable options for select circumstances with appropriate notifications of public health authorities. In this review, we will discuss briefly the virology, geographic distribution, diagnosis and management of monkeypox infection.

Anti- N-MethyL-D-Aspartate Receptor Encephalitis in Children Infected with Herpes Simplex

Herpes Simplex Virus (HSV) is a common cause of infectious encephalitis in children, which can lead to severe neurological sequels. There is a new perspective suggesting that herpes simplex encephalitis plays an important role in triggering the synthesis of NMDA receptor antibodies. There have been no data on the incidence of anti-NMDA receptor encephalitis in Indonesia. Herpes simplex encephalitis was found in these patients as a risk factor for anti-NMDA receptor encephalitis. A 9-year-old male patient complained of seizures such as jerking of the right hand and smacking of the lips along with fever for 4 days before being admitted to the hospital. Complaints began with slurred speech and t inability of fingers to hold objects for the previous 8 days. From the physical examination, it was reported that the patient looked seriously ill, blood pressure was 110/80 mmHg, pulse was 117 beats per minute, the temperature was 38.5 C, and respiratory rate was 24 times per minute. Another physical examination was within normal limits. The results of a complete blood count at the time of initial treatment of patients showed mild leukocytosis due to a mild increase in monocytes, whereas blood gas and electrolyte analysis showed hypoventilation at the beginning of hospitalization in which mixed acid-base disturbance, respiratory acidosis, and metabolic alkalosis occurred. Analysis of cerebrospinal fluid in these patients showed mononuclear pleocytosis and the results of immunoserological test in serum indicated HSV1 and HSV2 infection and detected anti-NMDA receptor. Both clinical and laboratory findings in this study supported encephalitis. Herpes simplex virus infection can be a risk factor for patients suffering from anti-NMDA receptor encephalitis.

Disseminated herpes simplex virus infection in immunocompetent patient

We describe an immunocompetent 49 years old male who presented with 5 days of fever &amp; anorexia that progressed to altered mentation and sever hepatitis. His CSF and blood viral PCR panel were positive for HSV-1.

Proliferating cell nuclear antigen inhibitors block distinct stages of herpes simplex virus infection.

Proliferating cell nuclear antigen (PCNA) forms a homotrimer that encircles replicating DNA and is bound by DNA polymerases to add processivity to cellular DNA synthesis. In addition, PCNA acts as a scaffold to recruit DNA repair and chromatin remodeling proteins to replicating DNA via its interdomain connecting loop (IDCL). Despite encoding a DNA polymerase processivity factor UL42, it was previously found that PCNA associates with herpes simplex virus type 1 (HSV-1) replication forks and is necessary for productive HSV-1 infection. To define the role that PCNA plays during viral DNA replication or a replication-coupled process, we investigated the effects that two mechanistically distinct PCNA inhibitors, PCNA-I1 and T2AA, have on the HSV-1 infectious cycle. PCNA-I1 binds at the interface between PCNA monomers, stabilizes the homotrimer, and may interfere with protein-protein interactions. T2AA inhibits select protein-protein interactions within the PCNA IDCL. Here we demonstrate that PCNA-I1 treatment results in reduced HSV-1 DNA replication, late gene expression, and virus production, while T2AA treatment results in reduced late viral gene expression and infectious virus production. To pinpoint the mechanisms by which PCNA inhibitors affect viral processes and protein recruitment to replicated viral DNA, we performed accelerated native isolation of proteins on nascent DNA (aniPOND). Results indicate that T2AA inhibits recruitment of the viral uracil glycosylase UL2 and transcription regulatory factors to viral DNA, likely leading to a defect in viral base excision repair and the observed defect in late viral gene expression and infectious virus production. In addition, PCNA-I1 treatment results in decreased association of the viral DNA polymerase UL30 and known PCNA-interacting proteins with viral DNA, consistent with the observed block in viral DNA replication and subsequent processes. Together, we conclude that inhibitors of cellular PCNA block recruitment of key viral and cellular factors to viral DNA to inhibit viral DNA synthesis and coupled processes.

Herpes Simplex Virus, Human Papillomavirus, and Cervical Cancer: Overview, Relationship, and Treatment Implications.

There is a significant body of research examining the role of human papillomavirus (HPV) in the pathogenesis of cervical cancer, with a particular emphasis on the oncogenic proteins E5, E6, and E7. What is less well explored, however, is the relationship between cervical cancer and herpes simplex virus (HSV). To date, studies examining the role of HSV in cervical cancer pathogenesis have yielded mixed results. While several experiments have determined that HPV/HSV-2 coinfection results in a higher risk of developing cervical cancer, others have questioned the validity of this association. However, clarifying the potential role of HSV in the pathogenesis of cervical cancer may have significant implications for both the prevention and treatment of this disease. Should this relationship be clarified, treating and preventing HSV could open another avenue with which to prevent cervical cancer. The importance of this is highlighted by the fact that, despite the creation of an effective vaccine against HPV, cervical cancer still impacts 604,000 women and is responsible for 342,000 deaths annually. This review provides an overview of HSV and HPV infections and then delves into the possible links between HPV, HSV, and cervical cancer. It concludes with a summary of preventive measures against and recent treatment advances in cervical cancer.

ICP8-vhs- HSV-2 Vaccine Expressing B7 Costimulation Molecules Optimizes Safety and Efficacy against HSV-2 Infection in Mice.

Herpes simplex virus 2 (HSV-2) causes most sexually transmitted genital ulcerative disease. No effective prophylactic vaccine is currently available. Replication-defective (ICP8-) HSV stimulates immune responses in animals without producing progeny virus, making it potentially useful as a safe form of a live vaccine against HSV. We previously demonstrated that mice generate a stronger response to ICP8- virus encoding B7-2 costimulation molecules than to the parental replication-defective virus. We have also demonstrated enhanced immunogenicity of an ICP8-, virion host shutoff (vhs)- virus which can no longer destabilize viral and host mRNAs. Here, we constructed a triple mutant, ICP8-vhs-B7-2+ strain, and compared it to both double mutant viruses. Immunization of mice with a single dose of ICP8-B7-2+ or ICP8-vhs-B7-2+ virus decreased challenge virus replication in the vaginal mucosa, genital disease, and mortality more effectively than immunization with the ICP8-vhs- virus. Immunization with ICP8-B7-2+ or ICP8-vhs-B7-2+ virus also effectively suppressed subsequent HSV-2 infection of the nervous system compared to immunization with the ICP8-vhs- virus. ICP8-B7-2+ and ICP8-vhs-B7-2+ strains induced more IFN gamma-producing CD8 T cells and memory CD8 T cells than did ICP8-vhs- virus, potentially explaining the enhanced protective effects. Thus, B7 costimulation molecules expressed from a replication-defective vaccine can enhance vaccine efficacy, even in an immunocompetent host.

A Comprehensive Review on HIV-Associated Dermatologic Manifestations: From Epidemiology to Clinical Management.

Dermatological disorders are among the most prevalent manifestations of HIV infection/acquired immunodeficiency syndrome (AIDS). In this review, we aimed to characterize the various dermatologic presentations among HIV-infected patients with a detailed categorization of the mucocutaneous signs and symptoms, their etiopathogenic factors, and clinical management. In fact, cutaneous manifestations of HIV are quite various, ranging from AIDS-specific skin eruptions (xerosis, pruritic papular eruptions, eosinophilic folliculitis, and acne), opportunistic infections (herpes simplex, molluscum contagiosum, cutaneous leishmaniasis, bacillary angiomatosis, disseminated histoplasmosis, disseminated cryptococcosis, and zoster) to AIDS-related malignancies (Kaposi's sarcoma, lymphoma, and nonmelanoma skin cancers) and antiretroviral therapy (ART)-associated drug eruptions. We tried to classify HIV-related cutaneous presentations which can help clinicians for a better understanding of the various specific and nonspecific features of AIDS-associated cutaneous manifestations and management of the condition.

Herpes simplex virus dissemination with necrotizing hepatitis following Descemet membrane endothelial keratoplasty

BackgroundCorneal transplants are the most common type of transplant and increasing in frequency. Donor cornea tissues are a rare source of herpes simplex virus (HSV) transmission and not routinely tested for presence of HSV. Donor graft-to-recipient transmission typically causes graft failure and anterior uveitis, and extra-ocular HSV disease has not been previously reported. We present a case of HSV transmission from donor cornea tissue that nearly cost the corneal transplant recipient his life.Case reportAn elderly immunocompetent man developed an acute illness 10 days after having donor corneal tissue implanted in a Descemet membrane endothelial keratoplasty (DMEK). He was found to have HSV necrotizing hepatitis per liver biopsy, trilineage cytopenia, rhabdomyolysis, acute kidney failure, altered mental status, early-stage hemophagocytic lymphohistiocytosis (HLH), and donor corneal tissue implant infection resulting in graft failure and anterior uveitis. HSV DNA was detected in cerebral spinal fluid, peripheral blood, explanted donor corneal tissue, and anterior chamber fluid (220 million HSV DNA copies per mL). HSV-1 seroconversion denoted a primary HSV infection, and the patient had no other risk factor for HSV acquisition. Early recognition of HSV dissemination prompting treatment with intravenous acyclovir, as well as a short course of HLH-directed therapy, resolved the systemic illness. Vision was restored to near normal by replacement of the infected corneal graft with new donor DMEK tissue in conjunction with intravitreal foscarnet treatment.ConclusionAwareness of the potential risk of donor cornea tissue transmitting HSV and leading to life-threatening HSV disease is paramount to early diagnosis and treatment. The role of donor cornea tissue in HSV transmission and disease merits additional attention and investigation.

Prior Herpes Simplex Virus Infection and the Risk of Herpes Zoster.

The incidence of herpes zoster (HZ) has increased in the United States concurrent with decrease in herpes simplex virus (HSV) prevalence. We hypothesized that lack of HSV-elicited cross-reactive immunity to varicella-zoster virus (VZV) results in an increased risk of HZ. Using specimens from the placebo arm of the Shingles Prevention Study, we investigated whether persons who develop HZ are less likely to have prior HSV infection than persons who do not develop HZ, and whether HZ is less severe in persons with HSV than in HSV seronegative persons. We conducted a nested case-control (1:2) study comparing the seroprevalence of HSV-1 and HSV-2 in cases (persons with polymerase chain reaction-confirmed HZ) to age-, sex-, and health-matched controls (persons without HZ). Sera from 639 study participants (213 cases and 426 controls) yielded definitive HSV antibody results and were analyzed. Overall, HSV seropositivity rate was 75%. HSV seronegativity was significantly higher in HZ cases than controls (30.5% vs 22.3%; P = .024), with a 55% higher risk of HZ in HSV seronegative than HSV seropositive participants. HSV seropositivity was associated with more severe HZ (P = .021). Our study demonstrated that prior infection with HSV partly protects against HZ.

Novel mutations in UL24 and gH rescue efficient infection of an HSV vector retargeted to TrkA

Transductional targeting of herpes simplex virus (HSV)-based gene therapy vectors offers the potential for improved tissue-specific delivery and can be achieved by modification of the viral entry machinery to incorporate ligands that bind the desired cell surface proteins. The interaction of nerve growth factor (NGF) with tropomyosin receptor kinase A (TrkA) is essential for survival of sensory neurons during development and is involved in chronic pain signaling. We targeted HSV infection to TrkA-bearing cells by replacing the signal peptide and HVEM binding domain of glycoprotein D (gD) with pre-pro-NGF. This TrkA-targeted virus (KNGF) infected cells via both nectin-1 and TrkA. However, infection through TrkA was inefficient, prompting a genetic search for KNGF mutants showing enhanced infection following repeat passage on TrkA-expressing cells. These studies revealed unique point mutations in envelope glycoprotein gH and in UL24, a factor absent from mature particles. Together these mutations rescued efficient infection of TrkA-expressing cells, including neurons, and facilitated the production of a completely retargeted KNGF derivative. These studies provide insight into HSV vector improvements that will allow production of replication-defective TrkA-targeted HSV for delivery to the peripheral nervous system and may be applied to other retargeted vector studies in the central nervous system.

The Association Between Female Genital Schistosomiasis and Other Infections of the Lower Genital Tract in Adolescent Girls and Young Women: A Cross-Sectional Study in South Africa.

This study aimed to explore the relationship between female genital schistosomiasis (FGS), sexually transmitted infections, bacterial vaginosis, and yeast among young women living in Schistosoma haematobium-endemic areas. In a cross-sectional study of young women, sexually active, aged 16 to 22 years in rural KwaZulu-Natal, South Africa, in 32 randomly selected rural schools in schistosomiasis-endemic areas, the authors performed gynecological and laboratory investigations, diagnosed FGS and other infections, and did face-to-face interviews. Female genital schistosomiasis was the second most prevalent current genital infection (23%), significantly more common in those who had urinary schistosomiasis (35%), compared with those without (19%, p < .001). In the FGS-positive group, 35% had human papillomavirus compared with 24% in the FGS-negative group (p = .010). In the FGS-positive group, 37% were seropositive for herpes simplex virus infection, compared with 30% in the FGS-negative group (p = .079). There were significantly fewer chlamydia infections among women with FGS (20%, p = .018) compared with those who did not have FGS (28%). Female genital schistosomiasis was the second most common genital infection after herpes simplex virus. Human papillomavirus infection was significantly associated with FGS, but Chlamydia was negatively associated with FGS. Women with FGS may have had more frequent contact with the health system for genital discharge. The results show the importance of the inclusion of FGS in the national management protocols for genital infections in areas endemic for S. haematobium and highlight a more comprehensive approach to diagnosis and genital disease management.