Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States.

CONTEXT: Herpes simplex virus type 1 (HSV-1) and type 2 are common infections worldwide. Herpes simplex virus type 2 (HSV-2) is the cause of most genital herpes and is almost always sexually transmitted. In contrast, HSV-1 is usually transmitted during childhood via nonsexual contacts. Preexisting HSV-1 antibodies can alleviate clinical manifestations of subsequently acquired HSV-2. Furthermore, HSV-1 has become an important cause of genital herpes in some developed countries. OBJECTIVE: To examine trends in HSV-1 and HSV-2 seroprevalence in the United States in 1999-2004 compared with 1988-1994. DESIGN, SETTINGS, AND PARTICIPANTS: Cross-sectional, nationally representative surveys (US National Health and Nutrition Examination Surveys [NHANES]), were used to compare national seroprevalence estimates from 1999-2004 with those from 1988-1994, and changes in HSV-1 and HSV-2 seroprevalence since 1976-1980 were reviewed. Persons aged 14 to 49 years were included in these analyses. MAIN OUTCOME MEASURES: Seroprevalence of HSV-1 and HSV-2 antibodies based on results from type-specific immunodot assays; diagnosis of genital herpes. RESULTS: The overall age-adjusted HSV-2 seroprevalence was 17.0% (95% confidence interval [CI], 15.8%-18.3%) in 1999-2004 and 21.0% (95% CI, 19.1%-23.1%) in 1988-1994, a relative decrease of 19.0% between the 2 surveys (95% CI, -28.6% to -9.5%; P<.001). Decreases in HSV-2 seroprevalence were especially concentrated in persons aged 14 to 19 years between 1988 and 2004. In adolescents aged 17 to 19 years and young adults, the decreases in HSV-2 seroprevalence were significant even after adjusting for changes in sexual behaviors. Among those infected with HSV-2, the percentage who reported having been diagnosed with genital herpes was statistically different (14.3% in 1999-2004 and 9.9% in 1988-1994; P = .02). Seroprevalence of HSV-1 decreased from 62.0% (95% CI, 59.6%-64.6%) in 1988-1994 to 57.7% (95% CI, 55.9%-59.5%) in 1999-2004, a relative decrease of 6.9% between the 2 surveys (95% CI, -11.6% to -2.3%; P = .006). Among persons infected with HSV-1 but not with HSV-2, a higher percentage reported having been diagnosed with genital herpes in 1999-2004 compared with 1988-1994 (1.8% vs 0.4%, respectively; P<.001). CONCLUSIONS: These data show declines in HSV-2 seroprevalence, suggesting that the trajectory of increasing HSV-2 seroprevalence in the United States has been reversed. Seroprevalence of HSV-1 decreased but the incidence of genital herpes caused by HSV-1 may be increasing.

Evolutionary-developmental perspectives on immune system interactions among the pregnant woman, placenta, and fetus, and responses to sexually transmitted infectious agents.

A balance has evolved over deep time between the various immune systems of the "triad" that is linked together for a short period: the pregnant woman, the fetus, and the placenta. This balance is affected by, and helps to determine, the immune responses to maternal infectious agents that may be transmitted to the fetus/infant transplacentally, intrapartum, or via breast milk. This review identifies newer evolutionary concepts and processes related particularly to the human placenta, innate and adaptive immune systems involved in tolerance, and in responses to sexually transmitted infectious (STI) agents that may be pathogenic to the fetus/infant at different gestational periods and in the first year of life. An evolutionary-developmental (EVO-DEVO) perspective has been applied to the complexities within, and among, the different actors and their beneficial or deleterious outcomes. Such a phylogenetic and ontogenic approach has helped to stimulate several basic questions and suggested possible explanations and novel practical interventions.

Prenatal exposure to maternal infections and epilepsy in childhood: a population-based cohort study.

OBJECTIVE: We estimated the association between prenatal exposure to maternal infections and the subsequent risk for epilepsy in childhood. METHODS: We included 90,619 singletons who were born between September 1997 and June 2003 in the Danish National Birth Cohort and followed them up to December 2005. Information on maternal infections during pregnancy (cystitis, pyelonephritis, diarrhea, coughs lasting >1 week, vaginal yeast infection, genital herpes, venereal warts, and herpes labialis) was prospectively reported by mothers in 2 computer-assisted telephone interviews in early and midgestation; information on maternal cystitis and pyelonephritis during late period of pregnancy was also collected in a third interview after birth. Children who received a diagnosis of epilepsy as inpatients or outpatients were retrieved from the Danish National Hospital Register. We identified 646 children with a diagnosis of epilepsy during up to 8 years of follow-up time. Cox proportional hazards regression models were used to estimate incidence rate ratio and 95% confidence interval. RESULTS: Children who were exposed to maternal cystitis, pyelonephritis, diarrhea, coughs, and/or vaginal yeast infection some maternal infections in prenatal life had an increased risk for epilepsy. Coughs lasting >1 week were associated with an increased risk for epilepsy only in the first year of life, as was vaginal yeast infection only in children who were born preterm. These associations remained unchanged for children without cerebral palsy, congenital malformation, or a low Apgar score at 5 minutes. CONCLUSIONS: Prenatal exposure to some maternal infections was associated with an increased risk for epilepsy in childhood.

Risk factors for incident herpes simplex type 2 virus infection among women attending a sexually transmitted disease clinic.

OBJECTIVES: To estimate the incidence of herpes simplex type 2 virus (HSV-2) infection, to identify risk factors for its acquisition, and to assess the protective effect of condoms. STUDY DESIGN: Prospective study of 293 HSV-2 seronegative women, aged 18 to 35 years, attending a sexually transmitted disease clinic in Alabama from 1992 to 1995. RESULTS: Incidence of HSV-2 infection was 20.5 per 100 woman-years [95% confidence interval (CI), 13.1-30.5]. Young women (18-20 years) had a significantly higher risk of incident HSV-2 infection [adjusted hazard ratio (HR), 2.8; 95% CI, 1.3-6.4] than older women. Women diagnosed with prevalent or incident bacterial vaginosis had a higher incidence of HSV-2 infection than those who were not so diagnosed (adjusted HR, 2.4; 95% CI, 1.1-5.6). No significant protective effect was observed for consistent (100%) condom use without breakage and slippage against HSV-2 acquisition (adjusted HR, 0.8; 95% CI, 0.2-2.3). CONCLUSION: Acquisition of HSV-2 infection among study participants was higher than previous estimates for adult female sexually transmitted disease clinic attendees, and no protective effect for condoms was demonstrated. The high incidence of HSV-2 infection with its potential for adverse health consequences emphasizes the need for better prevention strategies.

The possible role of transplacentally-acquired antibodies to infectious agents, with molecular mimicry to nervous system sialic acid epitopes, as causes of neuromental disorders: prevention and vaccine implications.

Proof of causality of most neuromental disorders (NMD's) is largely unavailable. Lessons from four-decade investigations of the epidemiology, immunology, pathogenesis, prevention and therapy of perinatal infectious agents, which invade directly the nervous system, have led us to propose a new indirect effect hypothesis: maternal transplacentally-acquired antibodies, to agents with epitope molecular mimicry with the developing nervous system, can cross the fetus/infant's blood-nervous system barriers to cause NMD's, clinically manifest years later. Further rationale is provided by relevant evolutionary/developmental (EVO-DEVO) considerations - applicable also to some vaccines. The hypothesis is being tested in: (a) older pregnancy studies with available maternal and newborn sera, and follow-up of the progeny for NMD's; and (b) NMD registry individuals linked to their stored newborn blood spots. Preliminary results support a possible role for schizophrenia of high-tittered antibodies to some agents (toxoplasma, influenza and herpes simplex type 2 virus). A model that includes likely genetic and postnatal influences is schematized and a list of putative agents and factors, based on varying rationales, is tabulated. In case pilot studies are confirmed, the identified agent(s) and antibodies would need to be tested in new prospectively enrolled pregnant women, so as to establish further risk factors leading to possible preventive modalities.

Cutting edge: antibody production to pneumococcal polysaccharides requires CD1 molecules and CD8+ T cells.

T cell involvement in Ab responses to thymus-independent type 2 Ags is an immunologic enigma. The identity of these cells and the mechanisms of their TCR engagement to carbohydrate molecules remain unknown. We measured IgG Ab production after immunization with pneumococcal polysaccharides in mice with disruptions in selected genes of the T cell pathway. Nonclassical MHC class I-like CD1 molecules and MHC class I-dependent CD8+ cells were found to be essential. Our findings set forth a new paradigm for humoral responses in which CD1 expression as well as a subset of CD8+ cells are required to provide helper function for Ab production against thymus-independent type 2 polysaccharides, similar to MHC class II-restricted CD4+ cells for protein Ags.

Neonatal HSV infection Part I: continuing challenges.

Neonatal herpes still presents diagnostic and management problems in view of continuing high mortality and morbidity rates, even though effective antiviral therapy is now available. This article, which reviews current knowledge and progress, provides practical guidelines for the diagnosis, management and treatment of neonatal herpes, based on the literature and decades of experience. It is advisable to focus at the local level on detecting maternal cervical infection, applying the available diagnostic tools and obtaining appropriate medical specialty consultations, as well as improving health worker and patient education about detecting and managing herpes simplex virus infections.

Neonatal HSV infection Part II: Obstetric considerations -- a tale of hospitals in two cities (Seattle and Atlanta, USA).

This article presents various aspects of maternal genital and neonatal herpes simplex virus (HSV)-1 and HSV-2 infection for hospitals in two cities in the USA - Seattle and Atlanta - to serve as models for the different subpopulations within developed and developing countries. Reasons are given for the disparity between the increasing rates of genital HSV-1 and HSV-2 infections observed in several areas of the world and the general low rates of newborn herpes noted in sites other than some hospitals in Seattle, Atlanta, Cincinnati and Helsinki. A key reason for the disparity appears to be the continuing difficulty in diagnosing maternal genital herpes and neonatal herpes. Contributing factors include the variability in different communities in sexual behaviour patterns, and in the rates of maternal genital HSV infection, caesarean sections and postmortem procedures. Unresolved challenges in the obstetric management of genital herpes aimed at preventing neonatal herpes are also presented.

Seroprevalence and coinfection with herpes simplex virus type 1 and type 2 in the United States, 1988-1994.

Seroprevalence of and coinfection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in the United States were analyzed by use of data from a nationally representative survey (National Health and Nutrition Examination Survey III, 1988-1994). Evidence was explored for possible protection by prior HSV-1 infection against infection and clinical disease with HSV-2. Overall, 27.1% of persons aged > or =12 years were seronegative for HSV-1 and HSV-2; 51.0% were seropositive for HSV-1 only, 5.3% for HSV-2 only, and 16.6% for both HSV-1 and HSV-2. The seroprevalence of HSV-2 was higher in persons with HSV-1 antibody. Approximately 76% of persons who had HSV-2 antibody also had HSV-1 antibody. Persons seropositive for HSV-2 only reported a history of genital herpes more frequently (16.2%) than persons seropositive for both HSV-1 and HSV-2 (5.9%). The seroprevalence of HSV-1 and age at infection may influence the epidemiology of clinical genital herpes, even if prior HSV-1 infection does not prevent HSV-2 infection.

Helicobacter pylori prevalence among indigenous peoples of South America.

The seroprevalence of Helicobacter pylori among secluded Indian populations of South America was determined to gain insight into the evolutionary history and possible transmission patterns of the organism. Serum samples obtained from 1024 donors in 22 different villages were tested by enzyme-linked immunosorbent assay for immunoglobulin G antibodies, and the results were confirmed by Western blot. The overall seroprevalence was 92%: >80% of children tested positive by 3 years of age, the highest prevalence in populations studied to date. Comparison of H. pylori prevalence with that of herpes simplex virus type 1, which is known to be transmitted orally, demonstrated a linear correlation in their prevalence rates, suggesting that these pathogens share risk factors. However, H. pylori seroprevalence was consistently higher, indicating that additional routes of transmission exist and/or that the organism is more transmissible. Seroprevalence did not correlate with the length of contact with the outside world. These results suggest that H. pylori was indigenous to the South American Indians and was not introduced by contact with outsiders.