Dual infection in pregnancy: Disseminated Mycoplasma hominis and necrotizing herpes simplex 2 hepatitis.

Mycoplasma hominis is part of the genitourinary flora in sexually active people and can cause disseminated infection in immunocompromised patients. We describe a rare case of an immunocompetent pregnant woman with simultaneous necrotizing HSV hepatitis and disseminated M. hominis infection. Detection of M. hominis and antimicrobial susceptibility testing of this fastidious organism in the clinical laboratory is discussed.

Glutamine supplementation suppresses herpes simplex virus reactivation.

Chronic viral infections are difficult to treat, and new approaches are needed, particularly those aimed at reducing reactivation by enhancing immune responses. Herpes simplex virus (HSV) establishes latency and reactivates frequently, and breakthrough reactivation can occur despite suppressive antiviral therapy. Virus-specific T cells are important to control HSV, and proliferation of activated T cells requires increased metabolism of glutamine. Here, we found that supplementation with oral glutamine reduced virus reactivation in latently HSV-1-infected mice and HSV-2-infected guinea pigs. Transcriptome analysis of trigeminal ganglia from latently HSV-1-infected, glutamine-treated WT mice showed upregulation of several IFN-γ-inducible genes. In contrast to WT mice, supplemental glutamine was ineffective in reducing the rate of HSV-1 reactivation in latently HSV-1-infected IFN-γ-KO mice. Mice treated with glutamine also had higher numbers of HSV-specific IFN-γ-producing CD8 T cells in latently infected ganglia. Thus, glutamine may enhance the IFN-γ-associated immune response and reduce the rate of reactivation of latent virus infection.

Intravaginal Zinc Oxide Tetrapod Nanoparticles as Novel Immunoprotective Agents against Genital Herpes.

Virtually all efforts to generate an effective protection against the life-long, recurrent genital infections caused by HSV-2 have failed. Apart from sexual transmission, the virus can also be transmitted from mothers to neonates, and it is a key facilitator of HIV coacquisition. In this article, we uncover a nanoimmunotherapy using specially designed zinc oxide tetrapod nanoparticles (ZOTEN) with engineered oxygen vacancies. We demonstrate that ZOTEN, when used intravaginally as a microbicide, is an effective suppressor of HSV-2 genital infection in female BALB/c mice. The strong HSV-2 trapping ability of ZOTEN significantly reduced the clinical signs of vaginal infection and effectively decreased animal mortality. In parallel, ZOTEN promoted the presentation of bound HSV-2 virions to mucosal APCs, enhancing T cell-mediated and Ab-mediated responses to the infection, and thereby suppressing a reinfection. We also found that ZOTEN exhibits strong adjuvant-like properties, which is highly comparable with alum, a commonly used adjuvant. Overall, to our knowledge, our study provides the very first evidence for the protective efficacy of an intravaginal microbicide/vaccine or microbivac platform against primary and secondary female genital herpes infections.

Genital herpes: a review.

Genital herpes simplex virus infection is a recurrent, lifelong disease with no cure. The strongest predictor for infection is a person's number of lifetime sex partners. The natural history includes first-episode mucocutaneous infection, establishment of latency in the dorsal root ganglion, and subsequent reactivation. Most infections are transmitted via asymptomatic viral shedding. Classic outbreaks consist of a skin prodrome and possible constitutional symptoms such as headache, fever, and inguinal lymphadenopathy. As the infection progresses, papules, vesicles on an erythematous base, and erosions appear over hours to days. These lesions usually crust, re-epithelialize, and heal without scarring. First-episode infections are more extensive: primary lesions last two to six weeks versus approximately one week for lesions in recurrent disease. Atypical manifestations are common. Infected persons experience a median of four recurrences per year after their first episode, but rates vary greatly. Genital herpes simplex virus type 2 recurs six times more frequently than type 1. Viral culture is preferred over polymerase chain reaction testing for diagnosis. Serologic testing can be useful in persons with a questionable history. Effective oral antiviral medications are available for initial, episodic, and suppressive therapy but are not a cure. There is some evidence that alternative therapies such as L-lysine, zinc, and some herbal preparations may offer some benefit. Counseling patients about the risk of transmission is crucial and helps prevent the spread of disease and neonatal complications.

Vitamin A supplementation and genital shedding of herpes simplex virus among HIV-1-infected women: a randomized clinical trial.

Cross-sectional analyses have associated vitamin A deficiency with genital shedding of herpes simplex virus (HSV) among human immunodeficiency virus type 1 (HIV-1)-infected women. A randomized clinical trial of vitamin A supplementation given daily for 6 weeks was conducted among 376 women in Mombasa, Kenya, who were coinfected with HSV-2 and HIV-1. At follow-up, there was no significant difference in the detection of genital HSV DNA between women receiving vitamin A supplementation and women receiving placebo (40% vs. 44%, respectively; P = .5) Among women shedding HSV, there was no significant difference in the mean HSV DNA quantity between the group that received vitamin A supplementation and the group that received placebo (4.51 vs. 4.67 log10 copies/swab; P = .6). HSV shedding was associated with significantly higher vaginal and cervical HIV-1 shedding, even after controlling for the plasma HIV-1 load and the CD4 count. Vitamin A supplementation is unlikely to decrease HSV shedding and infectivity.

Calcium phosphate nanoparticles induce mucosal immunity and protection against herpes simplex virus type 2.

Previously we reported that calcium phosphate nanoparticles (CAP) represented a superior alternative to alum adjuvants in mice immunized with viral protein. Additionally, we showed that CAP was safe and elicited no detectable immunoglobulin E (IgE) response. In this study, we demonstrated that following mucosal delivery of herpes simplex virus type 2 (HSV-2) antigen with CAP, CAP adjuvant enhanced protective systemic and mucosal immunity versus live virus. Mice were immunized intravaginally and intranasally with HSV-2 protein plus CAP adjuvant (HSV-2+CAP), CAP alone, phosphate-buffered saline, or HSV-2 alone. HSV-2+CAP induced HSV-specific mucosal IgA and IgG and concurrently enhanced systemic IgG responses. Our results demonstrate the potency of CAP as a mucosal adjuvant. Furthermore, we show that systemic immunity could be induced via the mucosal route following inoculation with CAP-based vaccine. Moreover, neutralizing antibodies were found in the sera of mice immunized intranasally or intravaginally with HSV-2+CAP. Also, the results of our in vivo experiments indicated that mice vaccinated with HSV-2+CAP were protected against live HSV-2 infection. In conclusion, these preclinical data support the hypothesis that CAP may be an effective mucosal adjuvant that protects against viral infection.

Daily or weekly therapy with resiquimod (R-848) reduces genital recurrences in herpes simplex virus-infected guinea pigs during and after treatment.

The effect of resiquimod (R-848), an immune-response modifier that is similar to imiquimod, on recurrent herpes simplex virus (HSV) was evaluated using the guinea pig model of genital herpes. Guinea pigs were intravaginally infected with HSV-2 and then were randomized on day 14 to receive nothing or 0.1 mL/kg per dose of subcutaneous resiquimod, given either daily, every other day, or weekly from days 15-35. During a 3-week course of therapy, recurrences in all 3 treated groups were reduced by >80%, compared with the control group. After therapy, recurrences remained significantly (P<.05) decreased in all 3 groups for the next 3 weeks. The group treated weekly developed the fewest recurrences. Significant increases in interleukin-2 levels, produced by incubation of mononuclear cells with HSV-2 antigens, but not in circulating antibody also were detected in the treated groups. Resiquimod treatment may offer significant advantages to present antiviral therapies for the control of recurrent genital herpes.

Does the extract of the plant Echinacea purpurea influence the clinical course of recurrent genital herpes?

An increasing proportion of the population perceive complementary medicine as a safer alternative for non-life threatening conditions such as genital herpes. The extract of the plant Echinacea purpurea (Echinaforce) has been shown to have immunomodulating properties and has been advocated in the lay press for the treatment of genital herpes. This study, a single centre, prospective, double blind, placebo-controlled cross-over trial set out to assess whether an extract of the plant and root of E. purpurea can prevent or decrease the frequency and severity of genital herpes recurrences. These were assessed using a detailed history and clinical review of symptoms. Visual analogue scales were used for documentation and haematological and immunological parameters were measured. Over a one-year period, 50 patients took part in the study receiving 6 months' placebo and 6 months' Echinaforce each. No statistically significant benefit could be detected in this study comparing placebo versus Echinaforce in the treatment of frequently recurrent genital herpes.

[Immune modulatory and therapeutical effect of shenqi tablet accessory therapy in treating recurrent genital herpes].

OBJECTIVE: To observe the immune modulatory and therapeutical effect of Shenqi tablet (SQT) in treating recurrent genital herpes. METHODS: Sixty-three patients were randomly divided into two groups, the SQT group (34 cases) and the control group (29 cases). The immunologic function of patients was determined before and after treatment and the recurrence rate of two groups was compared. RESULTS: In the SQT group after treatment, CD3, CD4 and CD4/CD8 ratio raised, CD8 percent lowered, serum interleukin 2 (SIL-2) and RBC-C3b raised and serum SIL-2 receptor lowered (all P < 0.05), while in the control group, the above-mentioned parameters were not changed significantly. Follow-up conducted 6 months after treatment showed that the recurrence rate in the SQT group was 26.5% (9 cases), which was lower than that in the control group (72.4%, 21 cases) significantly (P < 0.01). CONCLUSION: SQT has immune modulatory effect in patients with recurrent genital herpes, it could reduce the recurrence rate.

Calcium phosphate nanoparticle adjuvant.

Vaccination to protect against human infectious diseases may be enhanced by using adjuvants that can selectively stimulate immunoregulatory responses. In a murine model, a novel nanoparticulate adjuvant composed of calcium phosphate (CAP) was compared with the commonly used aluminum (alum) adjuvants for its ability to induce immunity to herpes simplex virus type 2 (HSV-2) and Epstein-Barr virus (EBV) infections. Results indicated that CAP was more potent as an adjuvant than alum, elicited little or no inflammation at the site of administration, induced high titers of immunoglobulin G2a (IgG2a) antibody and neutralizing antibody, and facilitated a high percentage of protection against HSV-2 infection. Additional benefits of CAP include (i) an insignificant IgE response, which is an important advantage over injection of alum compounds, and (ii) the fact that CAP is a natural constituent of the human body. Thus, CAP is very well tolerated and absorbed. These studies were performed with animal models. By virtue of the potency of this CAP adjuvant and the relative absence of side effects, we believe that this new CAP formulation has great potential for use as an adjuvant in humans.

Reductions in herpes simplex virus type 2 antibody titers after cognitive behavioral stress management and relationships with neuroendocrine function, relaxation skills, and social support in HIV-positive men.

OBJECTIVE: Coinfection with herpes simplex virus type 2 (HSV-2) is common in individuals infected with human immunodeficiency virus (HIV) and may have health implications. This study examined the effect of a 10-week cognitive behavioral stress management (CBSM) intervention on immunoglobulin G (IgG) antibody titers to HSV-2 in a group of mildly symptomatic HIV-infected gay men and the degree to which these effects were mediated by psychosocial and endocrine changes during the 10-week period. METHODS: Sixty-two HIV+ gay men were randomly assigned to either a 10-week CBSM intervention (N = 41) or a wait-list control condition (N = 21). Anxious mood, social support, cortisol/dehydroepiandrosterone sulfate (DHEA-S) ratio levels, and HSV-2 IgG antibody titers were assessed at baseline and after the 10-week period. CBSM participants also recorded their stress levels before and after at-home relaxation practice. RESULTS: HSV-2 IgG titers were significantly reduced in the CBSM participants but remained unchanged in the control group after the 10-week intervention period. Increases in one type of social support, perceived receipt of guidance, during the 10 weeks was associated with and partially mediated the effect of the intervention on HSV-2 IgG. Similarly, decreases in cortisol/DHEA-S ratio levels were associated with decreases in HSV-2 IgG, and lower mean stress levels achieved after home relaxation practice were associated with greater decreases in HSV-2 IgG among CBSM participants. CONCLUSIONS: These findings suggest that behavioral and psychosocial changes occurring during CBSM interventions, including relaxation, enhanced social support, and adrenal hormone reductions, may help to explain the effects of this form of stress management on immune indices such as HSV-2 antibody titers.

Immunological markers of frequently recurrent genital herpes simplex virus and their response to hypnotherapy: a pilot study.

Patients were recruited for hypnotherapy from a clinic for patients with frequently recurrent genital herpes simplex virus (rgHSV). Psychological and immunological parameters were measured 6 weeks prior to hypnotherapy and 6 weeks afterwards, during which time each patient kept a diary of symptoms of rgHSV. Following hypnotherapy there was a significant overall reduction in the number of reported episodes of rgHSV, accompanied by an increase in the numbers of CD3 and CD8 lymphocytes, which may represent a non specific effect of hypnosis. The improvers showed significant rises in natural killer (NK) cell counts, HSV specific lymphokine activated killer (LAK) activity, and reduced levels of anxiety when compared to non-improvers. NK cell numbers and HSV specific LAK activity may therefore be important in the reduction in rgHSV following hypnotherapy.

Oral famciclovir for suppression of recurrent genital herpes simplex virus infection in women. A multicenter, double-blind, placebo-controlled trial. Collaborative Famciclovir Genital Herpes Research Group.

OBJECTIVE: To evaluate the efficacy and safety of oral famciclovir in the suppression of genital herpes. METHODS: In this randomized, double-blind, placebo-controlled trial that was performed at 11 university and 9 private ambulatory care referral centers, 375 women who were 18 years of age or older and had a history of 6 or more episodes of genital herpes during 12 of the last 24 months in the absence of suppressive therapy were treated for 4 months with oral famciclovir, 125 mg once daily or twice daily, 250 mg once daily or twice daily, 500 mg once daily, or placebo. The primary outcome measures included the time to first clinically and virologically confirmed recurrences, and safety as measured by clinical laboratory tests and adverse experiences. RESULTS: The median time to first recurrence was 82 days in the placebo group, 114 days in those receiving famciclovir, 125 mg once daily, and more than 120 days in the other treatment groups. When compared with placebo recipients, the time to the first clinical recurrence was significantly prolonged in subjects who received famciclovir, 125 mg twice daily (hazard ratio, 1.8; 95% confidence interval, 1.0-3.0; P = .03), and in those who received famciclovir, 250 mg twice daily (hazard ratio, 3.6; 95% confidence interval, 1.9-6.9; P < .001). Treatment was well tolerated, and there was no evidence of emergence of resistance during or after suppressive famciclovir therapy. CONCLUSIONS: Oral famciclovir, 250 mg, given twice daily for 4 months is an effective, well-tolerated treatment for the suppression of genital herpes in women with frequent recurrences, but single daily doses produced less complete suppression of genital herpes.

Role of complement inhibition in topical therapy of muco-cutaneous herpes simplex virus infections.

A complement-inhibiting formulation with anti-inflammatory activity due to suppression of both the classical and alternative pathways of complement activation is presented for local treatment of muco-cutaneous lesions produced by Herpes simplex virus, types 1 and 2. The drug contains glutaraldehyde, a strong inhibitor of the complement system, dimethylsulphoxyde, used as a vector modifying the barrier properties of the skin and 1,2-propylene glycol, a delipidating agent which increases the adhesiveness of the watery solutions to the skin surface. It proved to be devoid of adverse effects for normal skin of animal and humans, and produced rapid disappearance of herpetic neuralgia and accelerates the remission of local symptoms. The mechanism of action seems to be associated with the inhibition of local anaphylatoxin release (C3a and C5a) which are responsible for the acute evolution of the lesions produced by viruses of the Zoster-Varicella group and with a quick lethal effect on the parasitized cells which are selectively eliminated without affecting the adjoining normal cells of the host.

Stress, emotion, and human immune function.

This article provides a review of empirical evidence linking emotional processes to immune function in humans. Acute stressors have produced mixed effects on immunity, presumably through differential activation of physiological stress systems. Chronic stress has been associated with suppression of immune function, and there is evidence that the immune system may not adapt over time. Effects of stress accompanying social disruption and psychological depression, when demonstrated, have been consistently adverse. Certain personality styles may enhance or degrade immune response. Relationships between psychosocial factors and immunity have been identified for several diseases, including cancer, acquired immune deficiency syndrome, and autoimmune diseases; psychosocial interventions have been tested with variable results. Theoretical and methodological considerations are summarized and directions for future research suggested.