Treatment of herpes simplex labialis.

Journal ArticleRecurrent herpes simplex labialis is associated with mild morbidity, but remains a significant problem for people with frequent and/or severe recurrences. Both topical and peroral episodic antiviral treatments of recurrences are modestly effective at reducing the duration of signs and symptoms. Recent studies with high-dose, short-course valaciclovir suggest that maximum benefit from antiviral therapy may be achieved with as little as 1 day of treatment. Topical steroids may be useful in combination with an antiviral agent, but more needs to be learnt about the appropriate strength and duration of steroid therapy before a general recommendation can be made. Selected subgroups of patients are candidates for prophylactic treatment with perorally administered nucleoside antiviral agents. Prophylaxis with topical agents is not effective

Helicase-primase inhibitor pritelivir for HSV-2 infection

pre-printBackground Pritelivir, an inhibitor of the viral helicase-primase complex, exhibits antiviral activity in vitro and in animal models of herpes simplex virus (HSV) infection. We tested the efficacy and safety of pritelivir in otherwise healthy persons with genital HSV-2 infection. Methods We randomly assigned 156 HSV-2-positive persons with a history of genital herpes to receive one of four doses of oral pritelivir (5, 25, or 75 mg daily, or 400 mg weekly) or placebo for 28 days. Participants obtained daily swabs from the genital area for HSV-2 testing, which was performed with a polymerase-chain-reaction assay. Participants also maintained a diary of genital signs and symptoms. The primary end point was the rate of genital HSV shedding. Results HSV shedding among placebo recipients was detected on 16.6% of days; shedding among pritelivir recipients was detected on 18.2% of days among those receiving 5 mg daily, 9.3% of days among those receiving 25 mg daily, 2.1% of days among those receiving 75 mg daily, and 5.3% of days among those receiving 400 mg weekly. The relative risk of viral shedding with pritelivir, as compared with placebo, was 1.11 (95% confidence interval [CI], 0.65 to 1.87) with the 5-mg daily dose, 0.57 (95% CI, 0.31 to 1.03) with the 25-mg daily dose, 0.13 (95% CI, 0.04 to 0.38) with the 75-mg daily dose, and 0.32 (95% CI, 0.17 to 0.59) with the 400-mg weekly dose. The percentage of days with genital lesions was also significantly reduced, from 9.0% in the placebo group to 1.2% in both the group receiving 75 mg of pritelivir daily (relative risk, 0.13; 95% CI, 0.02 to 0.70) and the group receiving 400 mg weekly (relative risk, 0.13; 95% CI, 0.03 to 0.52). The rate of adverse events was similar in all groups

Nucleic acid vaccine encoding gD2 protects mice from herpes simplex virus type 2 disease.

Journal ArticleNucleic acid vaccinations with plasmids pWW65, containing the sequence for herpes simplex type 2 (HSV-2) gD2, and pRSVnt, lacking the gD sequence, were studied. Groups of mice were immunized with pWW65 alone, pWW65 plus 1,25-dihydroxyvitamin-D3 (D3), or pRSVnt. Clinical disease (vaginitis), serum and vaginal washing antibody levels, and vaginal washing virus titers were measured intravaginal HSV-2 challenge. No animals (0/10) in the pWW65 + D3 group, 6/10 animals in the pWW65 group, and 10/10 animals in the pRSVnt group developed severe disease by postchallenge day 13 (P<.001, P=.04 vs. pRSVnt). Virus titers in vaginal washings were significantly reduced in the pWW65 and pWW65+D3 groups versus the pRSVnt group (P<.001). Increasing levels of serum anti-gD2 antibodies were measured 2 and 6 days after challenge among animals in the pWW65 and pWW65+D3 groups but not among animals in the pRSVnt group. Vaccinations with a plasmid containing the gD2 gene are immunogenic and provide some protection from HSV-2-induced disease

Correlation between detection of herpes simplex virus in oral secretions by PCR and susceptibility to experimental UV radiation-induced herpes labialis.

Journal ArticleWe examined the oral secretions of 25 patients for herpes simplex virus (HSV) at the time of and following experimental UV radiation (UVR). HSV was detected in one or more oral secretion specimens in 5 of 12 (42%) cases by cell culture and in 8 of 12 (67%) cases by PCR. On the day of UVR, HSV was detected in 1 of 12 (8%) patients who developed a lip lesion and 2 of 16 (13%) patients who did not (the difference is not significant). We conclude that PCR is more sensitive than culture in the detection of HSV and that HSV is not shed with increased frequency from the oral cavity before the development of UVR-induced herpes labialis

Invasive sinonasal disease due to Scopulariopsis candida: case report and review of scopulariopsosis.

Journal ArticleSinonasal infection with fungi of the order Mucorales--termed mucormycosis or zygomycosis--is sometimes seen in immunosuppressed patients, including those with diabetic ketoacidosis and malignancy. We describe a case of invasive sinonasal infection with Scopulariopsis candida (not among the Mucorales organisms) in a 12-year-old girl who was being treated for non-Hodgkin's lymphoma. Only a few cases of invasive infection with Scopulariopsis species have been reported previously; five of six of these cases were associated with persistent or fatal disease. Our patient survived without undergoing radical surgical debridement and was treated with granulocyte colony-stimulating factor, amphotericin B, and itraconazole; chemotherapy was stopped. In vitro susceptibility testing of our patient's Scopulariopsis isolate showed that it was resistant to amphotericin B and that it was relatively susceptible to itraconazole and miconazole. The case described herein demonstrates the expanding spectrum of fungal organisms that may cause invasive sinonasal infection in immunocompromised hosts and the need for reliable antifungal susceptibility testing

Miliary Tuberculosis and the postpartum state

Journal ArticleIn 1985, a resurgence of tuberculosis began in the United States. In conjunction with this resurgence, there has been an increase in the number of atypical presentations of the disease. We recently treated a patient who had disseminated tuberculosis that became manifest in the postpartum state. Whereas postpartum progression of tuberculosis was a well-recognized clinical entity in the preantibiotic era, few reports have dealt with the issue recently. We present this case as a timely reminder of the many faces of tuberculosis

Spinal fluid IgG antibodies from patients with demyelinating diseases bind multiple sclerosis-associated bacteria

ABSTRACT: A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases (DD). The anti-microbial ELISA assays follow on prior human brain tissue RNA sequencing studies that established multiple sclerosis (MS) microbial candidates. Lysates included in the ELISA panel were derived from Akkermansia muciniphila, Atopobium vaginae, Bacteroides fragilis, Lactobacillus paracasei, Odoribacter splanchnicus, Pseudomonas aeruginosa, Cutibacterium (Propionibacterium) acnes, Fusobacterium necrophorum, Porphyromonas gingivalis, and Streptococcus mutans. CSF responses from patients with demyelinating diseases (DD, N = 14) were compared to those with other neurological diseases (OND, N = 8) and controls (N = 13). Commercial positive and negative control CSF specimens were run with each assay. ELISA index values were derived for each specimen against each of the 10 bacterial lysates. CSF reactivity was significantly higher in the DD group compared to the controls against Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Four of the 11 tested DD group subjects had elevated antibody indexes against at least one of the 10 bacterial species, suggesting intrathecal antibody production. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients. KEY MESSAGES: A panel of 10 IgG enzyme-linked immunosorbent assays (ELISAs) were developed for the detection of anti-microbial immune responses in the cerebrospinal fluid (CSF) of patients with demyelinating diseases, including multiple sclerosis and acute disseminated encephalomyelitis. CSF reactivity was significantly higher in the demyelination group compared to the controls against the bacteria Akkermansia, Atopobium, Bacteroides, Lactobacillus, Odoribacter, and Fusobacterium. Several of the demyelination subjects had elevated antibody indexes against at least one of the 10 antigens, suggesting at least limited intrathecal production of anti-bacterial antibodies. This CSF serological study supports the hypothesis that several of the previously identified MS candidate microbes contribute to demyelination in some patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00109-021-02085-z

Anti-interleukin-6 antibodies inhibit herpes simplex virus reactivation.

Journal ArticleHerpes simplex viruses (HSVs) infect epithelial cells, become localized in neurons, and can reactivate in response to a variety of stimuli, including ultraviolet light and hyperthermia. The sequence of gene activation during viral replication is known, but the molecular linkage between exogenous stimuli and HSV reactivation has not been determined. It was hypothesized that interleukin (IL)-6 acts as a signal between exogenous stimuli and neurons, stimulating HSV reactivation from latency. Mouse corneas were infected with HSV-1, and ocular reactivation was induced 5-7 weeks later by thermal stress or corneal exposure to ultraviolet light. Anti-IL-6 monoclonal antibodies were administered to the latently infected mice 8-12 h before the reactivation stimulus. Treatment with anti-IL-6 antibodies resulted in significantly lower frequencies of ocular reactivation compared with those in mice treated with a control immunoglobulin. These results support the hypothesis that IL-6 plays a role in HSV reactivation from latency

Rocky Mountain spotted fever following cardiac transplantation.

Journal ArticleROCKY MOUNTAIN SPOTTED FEVER was first recognized in the early 1 900s in the Snake River Valley of Idaho and the Bitterroot Valley of western Montana.t In 1909, Howard Taylor Ricketts established the ixodid tick as the vector for the disease.2 Following the tick bite, the incubation period averages seven days (4 to 10 days), and the disease varies in severity and course. Typically a patient's temperature remains elevated to 39°C to 400C (102OF to 1040F). A characteristic rash, a relatively late manifestation, may appear on the wrists and ankles and extend throughout the body, including the palms and soles. Initially there are erythematous macules that blanch with pressure, but after several days the rash becomes maculopapular and petechial. The rash begins to clear as the fever resolves, but lesions may remain visible for as long as several weeks. Widespread vascular damage may occur involving the skin, lungs, heart (myocarditis), brain, pancreas, liver, skeletal muscle, or kidneys. The endothelial cell injury leads to increased vascular permeability, edema, hypovolemia, and hypotension.