Pseudoepitheliomatous hyperplasia causing a painful plaque in a HIV-infected female.

Dermatological conditions are more common and can present atypically, in human immunodeficiency virus-infected individuals. This case report describes a 22-year-old human immunodeficiency virus-positive Caucasian female who presented with a vulval lesion eight weeks after starting antiretroviral treatment. Clinical examination revealed a 2 cm well-demarcated plaque on the outer aspect of the left labium minus. The lesion was tender, no contact bleeding or ulceration present. She was presumptively treated for chancroid and herpes simplex with 500 mg ceftriaxone IM stat, 1 g azithromycin PO stat, and valacyclovir 500 mg BD for five days. The lesion persisted despite treatment, and during follow-up, a punch biopsy was carried out. She was diagnosed with pseudoepitheliomatous hyperplasia of the epidermis. In addition to highlighting this condition that has been previously reported in human immunodeficiency virus/herpes simplex virus co-infection, this case demonstrates that unusual skin presentations must be considered in human immunodeficiency virus-infected individuals and illustrates the importance of biopsy for any non-healing lesions.

Association of HPV infection and clearance with cervicovaginal immunology and the vaginal microbiota.

Cervical human papillomavirus (HPV) infection may increase HIV risk. Since other genital infections enhance HIV susceptibility by inducing inflammation, we assessed the impact of HPV infection and clearance on genital immunology and the cervico-vaginal microbiome. Genital samples were collected from 65 women for HPV testing, immune studies and microbiota assessment; repeat HPV testing was performed after 6 months. All participants were HIV-uninfected and free of bacterial STIs. Cytobrush-derived T cell and dendritic cell subsets were assessed by multiparameter flow cytometry. Undiluted cervico-vaginal secretions were used to determine cytokine levels by multiplex ELISA, and to assess bacterial community composition and structure by 16S rRNA gene sequence analysis. Neither HPV infection nor clearance were associated with broad differences in cervical T cell subsets or cytokines, although HPV clearance was associated with increased Langerhans cells and HPV infection with elevated IP-10 and MIG. Individuals with HPV more frequently had a high diversity cervico-vaginal microbiome (community state type IV) and were less likely to have an L. gasseri predominant microbiome. In summary, HPV infection and/or subsequent clearance was not associated with inflammation or altered cervical T cell subsets, but associations with increased Langerhans cells and the composition of the vaginal microbiome warrant further exploration.

CD18 deficiency evolving to megakaryocytic (M7) acute myeloid leukemia: case report.

Leukocyte adhesion deficiency type 1 (LAD 1 - CD18 deficiency) is a rare disease characterized by disturbance of phagocyte function associated with less severe cellular and humoral dysfunction. The main features are bacterial and fungal infections predominantly in the skin and mucosal surfaces, impaired wound healing and delayed umbilical cord separation. The infections are indolent, necrotic and recurrent. In contrast to the striking difficulties in defense against bacterial and fungal microorganisms, LAD 1 patients do not exhibit susceptibility to viral infections and neoplasias. The severity of clinical manifestations is directly related to the degree of CD18 deficiency. Here, a 20 year-old female presenting a partial CD18 deficiency that developed a megakaryocytic (M7) acute myeloid leukemia is described for the first time. The clinical features of the patient included relapsing oral thrush due to Candida, cutaneous infections and upper and lower respiratory tract infections, followed by a locally severe necrotic genital herpetic lesion. The patient's clinical features improved for a period of approximately two years, followed by severe bacterial infections. At that time, the investigation showed a megakaryocytic acute myeloid leukemia, treated with MEC without clinical improvement. The highly aggressive evolution of the leukemia in this patient suggests that adhesion molecules could be involved in the protection against the spread of neoplastic cells.

Vulvar pseudoepitheliomatous hyperplasia associated with herpes simplex virus type II mimicking cancer in an immunocompromised patient.

We report an exaggerated dermatological inflammatory condition in an immunocompromised patient. The patient was a 51-year-old woman who had HIV infection and a history of cervical cancer. Three years after highly active antiretroviral therapy with an improved immune status, and 2 years after remission of cervical cancer, she developed verrucous perineal masses. Provisional diagnosis was recurrent cervical cancer or primary vulvar cancer. Pathological features revealed pseudoepitheliomatous hyperplasia associated with herpes viral infection. After minimal response to systemic oral antiviral drugs and topical imiquimod, she had clinical resolution with the addition of systemic oral corticosteroid.

[Comprehensive examination of the female urogenital tract infection by polymerase chain reaction using multiplex test systems].

The results of the polymerase chain reaction studies performed in 2006-2008 were used to make a retrospective analysis of the detection of urogenital herpesvirus infections in reproductive-aged women constituting the urban population of the central region of Russia. The study used both monotarget and mutiplex test systems to detect herpes simplex virus (HSV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus types 6 and 7. A total of about 7.500 referrals; the detection rate for HSV was about 1%; that for CMV was from 0.3 in 2006 to 1% in 2008; that for EBV was from 0.1% in 2006 to 0.3% in 2008. More than a half of HSV-, CMV-, or EBY-positive samples also contained DNA of other causative agents and some samples did two pathogens or more. Multiplex test systems for herpesviruses considerably enhance the efficiency of diagnostic studies and reduce the material and time costs of diagnosis.

Herpes simplex virus type 2 and Chlamydia trachomatis in adenocarcinoma of the uterine cervix.

INTRODUCTION: Adenocarcinoma of the uterine cervix (AC) occurs in 15-20% of primary cervical neoplasias. Although some etiologic factors for squamous cell carcinoma are well defined, and its relationship with sexually transmitted disease as human papillomavirus (HPV) is established, we still do not know about the causative factors of most of AC besides HPV infection. OBJECTIVES: To determine the presence of herpes simplex virus type 2 (HSV-2) and Chlamydia trachomatis (CT) DNA in AC specimens, and its correlation with HPV infection. METHODS: 206 paraffin-embedded cases of AC were selected to DNA extraction. The specimens and the DNA were isolated. Samples were first screened for beta-globin DNA sequences, and 67 cases were considered adequate to further analysis. In a previous analysis, DNA of HPV was identified in 79.4% of specimens included in this series (51% HPV 18 and 34% HPV 16). The local ethical committee approved the study. RESULTS: All samples were negative for HSV-2 DNA and CT DNA. CONCLUSIONS: In our series HSV-2 DNA and CT DNA were not found to be integrated to the genome of adenocarcinoma of the uterine cervix and do not seem to be a co-factor for HPV on the etiology of this histologic subtype.

Sexually transmitted infections in men.

The diagnosis and treatment of STDs is a common problem in primary care practice; however, newer diagnostic and therapeutic alternatives require physicians to be aware of evidence-based guidelines that are continuing to evolve. The treatment of STDs in men, in particular, is an area of evolving evidence because much of what is known is based on the treatment of STDs in women. Men represent unique challenges in diagnosis, evaluation, and follow-up that need to be considered in the treatment of urethritis, epididymitis, herpes genitalis, condyloma, prostatitis, and other syndromes. Screening for asymptomatic STDs is currently not recommended in the general population, but selected criteria can be used to identify a target population for screening in high-risk areas.

The association of herpes simplex virus type 2 (HSV-2), Haemophilus ducreyi, and syphilis with HIV infection in young men in northern Thailand.

To evaluate the association between sexually transmitted diseases that commonly may cause genital ulceration and prevalent and incident HIV infections, we conducted three case control studies in a cohort of 21-year-old male military conscripts in northern Thailand. The men were evaluated at baseline in 1991 and semiannually until their discharge 2 years later. Serologic evidence of infection with herpes simplex virus type 2 (HSV-2), Haemophilus ducreyi, and HIV were more frequent at baseline in 83 men with a history of genital ulcer than in 97 men without such a history. Seropositivity to H. ducreyi (odds ratio [OR] = 3.46), HSV-2 (OR = 3.83), and syphilis (OR = 1.53) were more common in HIV-positive than HIV-negative men. Men (N = 45) who seroconverted to HIV while in the military were more often seropositive for H. ducreyi and HSV-2 before HIV seroconversion and also were more likely to seroconvert to HSV-2 and H. ducreyi during the same interval as their HIV seroconversion compared with men who remained HIV-negative. These data suggest that HSV-2 and H. ducreyi may be both markers for high-risk sexual behavior and risk factors for HIV infection among young men in Thailand.

PIP: Three case-control studies conducted in 1991-93 in a cohort of 21-year-old male military conscripts in northern Thailand investigated the association between HIV infection and three sexually transmitted diseases (STDs) commonly associated with genital ulceration: herpes simplex virus type 2 (HSV-2), Haemophilus ducreyi, and Treponema pallidum. The studies compared 83 men with a history of genital ulcer disease (GUD) at baseline and 97 men without such a history, 103 men who were HIV-positive at baseline and 110 randomly selected HIV-negative conscripts, and 45 men who seroconverted to HIV while they were in the military and 124 men who remained HIV-negative throughout military service. The first study detected a significant dose-response association between number of commercial sex worker visits in the past year, lifetime number of sexual partners, and a history of GUD. Among men with GUD at baseline compared with those without GUD, the odds ratios were 2.52 for HSV-2, 2.02 for H. ducreyi, 0.97 for syphilis, and 2.14 for HIV. In the second study, HIV-infected men were significantly more likely than HIV-negative men to have antibodies to HSV-2 and H. ducreyi and a history of syphilis or gonorrhea. In the third study, men who converted to HIV were significantly more likely to have antibodies to H. ducreyi and HSV-2 at the visit before seroconversion than those who remained HIV-negative. Two independent predictors of seroconversion--HSV-2 seropositivity before conversion and 10 or more lifetime sexual partners--were identified. In northern Thailand, GUD, especially H. ducreyi and HSV-2, may be both a marker for increased HIV risk and a cofactor for HIV transmission.

Expression of the herpes simplex virus type 2 latency-associated transcript enhances spontaneous reactivation of genital herpes in latently infected guinea pigs.

The latency-associated transcript (LAT) is the only herpes simplex virus (HSV) gene product detectable in latently infected humans and animals. In this report, we show that a 624-bp deletion in the promoter of the HSV-2 LAT had no discernable effect on viral growth in tissue culture or in acute genital infection of guinea pigs, but impaired LAT accumulation and led to a marked decrease in spontaneous genital recurrences when compared with the behavior of wild-type and rescuant strains. Differences in the ability of the mutant to replicate, or in how readily it established or maintained latency did not account for this finding. Thus, HSV LAT expression facilitates the spontaneous reactivation of latent virus.

Simple algorithms for the management of genital ulcers: evaluation in a primary health care centre in Kigali, Rwanda.

A cross-sectional study was conducted among 395 patients presenting with genital ulcers at a primary health care centre in Kigali, Rwanda. Using clinical data and the results of a rapid plasma reagin (RPR) test, we simulated the diagnostic outcome of two simple WHO flowcharts for the management of genital ulcers. These outcomes and a clinical diagnosis were then compared with the laboratory diagnosis based on culture for genital herpes and Haemophilus ducreyi and serology for syphilis. The prevalence of HIV infection was high (73%) but there was no difference between HIV-positive and HIV-negative patients in the clinical presentation and etiology of genital ulcer disease. The proportion of correctly managed chancroid and/or syphilis cases was 99% using a syndromic approach, 82.1% using a hierarchical algorithm including an RPR test, and 38.3% with a clinical diagnosis. In situations where no laboratory support is available, a simple syndromic approach is preferable to the clinical approach for the management of genital ulcer. If an RPR test can be included in the diagnostic strategy, patients with a reactive RPR test should be treated for both syphilis and chancroid infection.

PIP: A cross-sectional study was conducted among 395 patients presenting with genital ulcers at a primary health care center in Kigali, Rwanda. Using clinical data and the results of a rapid plasma reagin (RPR) test, the authors simulated the diagnostic outcome of two simple WHO flowcharts for the management of genital ulcers. These outcomes and a clinical diagnosis were then compared with the laboratory diagnosis based on culture for genital herpes and Haemophilus ducreyi and serology for syphilis. The prevalence of HIV infection was high (73%) but there was no difference between HIV-positive and HIV-negative patients in the clinical presentation and etiology of genital ulcer disease. The proportion of correctly managed chancroid and/or syphilis cases was 99% using a syndromic approach, 82.1% using a hierarchical algorithm including an RPR test, and 38.3% with a clinical diagnosis. In situations where no laboratory support is available, a simply syndromic approach is preferable to the clinical approach for the management of genital ulcer. If an RPR test can be included in the diagnostic strategy, patients with a reactive RPR test should be treated for both syphilis and chancroid infection. (author's)

Quantity of latency-associated transcript produced by herpes simplex virus is not predictive of the frequency of experimental recurrent genital herpes.

The role of the latency-associated transcript (LAT) in control of recurrent herpes simplex virus type 2 (HSV-2) infection was investigated by examining whether LAT concentration in vitro during productive infection or in ganglia during latency correlated with frequency of recurrent genital herpes. Clinical HSV-2 isolates from frequent or infrequent recurrent genital disease produced comparable amounts of glycoprotein D and infected cell polypeptide 0 RNA, but the isolate from frequent disease produced about seven times more LAT. The guinea pig model of genital herpes was used to determine whether the quantity of LAT produced during acute infection in vitro correlated with recurrence phenotype; the frequency of recurrent disease was similar for the 2 clinical isolates. Likewise, there was no correlation between the recurrence phenotype of individual animals and LAT concentration in their ganglia. Thus, while absence of LAT may impair HSV reactivation and recurrence, once a threshold concentration is exceeded, LAT has no further effect on recurrence frequency.

A rapid simple in situ hybridization method for herpes simplex virus employing a synthetic biotin-labeled oligonucleotide probe: a comparison with immunohistochemical methods for HSV detection.

We examined 28 paraffin-embedded tissue specimens with histologic evidence of herpes virus infection by in situ hybridization (ISH) utilizing manual capillary action technology (MicroProbe Staining System) and a 21 base synthetic multibiotinylated oligonucleotide probe from the HSV glycoprotein C region. The results were compared to a rapid simple immunohistochemical (IHC) protocol for detection of HSV proteins. HSV was detected by ISH and IHC in all but one specimen which was shown to be positive for varicella zoster virus by direct fluorescent antibody studies. Hybridization signal was confined to the nucleus in all cases. Staining was identified in cells with early as well as late cytopathic effect. IHC produced intense nuclear and/or cytoplasmic signal in infected cells and stained in areas of necrosis which were otherwise spared by ISH. HSV was detected by IHC and/or ISH in 3/5 specimens with histology suggestive of, but not diagnostic for, HSV infection. Both techniques were sensitive and specific for HSV, resulted in rapid detection of the pathogen in routinely processed tissues, and may be useful in cases where the histologic impression is equivocal for HSV infection. ISH for HSV may be preferred because it can identify early HSV infection, which in turn can be treated with antiviral agents.

Evaluation of a monoclonal antibody-based enzyme immunoassay for early detection of herpes simplex virus genital infection.

A monoclonal antibody-based enzyme immunoassay test for detection of herpes simplex virus (HSV) type-common antigen was evaluated in 40 women with vulvar lesion suspicious for genital HSV infection. The assay gave interpretable readings in 90% of the cases, with sensitivity and specificity of 100% and 92% respectively, a negative predictive value of 100%, and a positive predictive value of 75%. With a few limitations, the assay may be used for early diagnosis of genital HSV infection.

Herpes simplex virus detection from genital lesions: a comparative study using antigen detection (HerpChek) and culture.

The sensitivity of a rapid enzyme immunoassay test (HerpChek Direct Herpes Simplex Virus Antigen Test [DuPont Medical Products, Wilmington, Del.]) for the detection of herpes simplex virus (HSV) antigens in patient specimens was compared with HSV culture. HerpChek positivity for HSV occurred with 179 (65%) of 275 lesion specimens, whereas culture for HSV was positive for 145 (53%) lesions (P = 0.002). HerpChek was twice as sensitive as culture for the detection of HSV in late-stage lesions and was equivalent to culture for the detection of HSV in early lesions. We conclude that HerpChek provides greater sensitivity than culture for HSV detection in late-stage genital lesions.

[Ileocolitis caused by Herpes simplex virus type 2]. / Iléo-colite herpétique à virus Herpes simplex de type 2.

The authors report the case of a 51-year-old woman who was hospitalized for severe acute colitis. Sub-total colectomy was performed, due to clinical deterioration and resistance to treatment. The examination of the surgery specimen revealed a herpes-virus type 2 as the responsible pathogen agent. Complementary aciclovir treatment cured the patient.

A point mutation in the thymidine kinase gene is responsible for acyclovir-resistance in herpes simplex virus type 2 sequential isolates.

A number of HSV-2 isolates, sequentially recovered from ulcerative ano-genital lesions of an AIDS patient during a prolonged treatment with acyclovir (ACV), have been studied at the molecular level. All of them were highly resistant to ACV (ACV-r) and shown to be virtually deficient in thymidine kinase (TK) activity. The ACV-r phenotype was demonstrated to be due to the production of truncated TK polypeptide. Structural alteration of this gene, as shown in one isolate, was caused by a chain-terminating mutation that originated from a cytidine deletion at position 520 of the TK open reading frame. This mutation generated a TGA stop codon 27 nucleotides downstream. An additional isolate was also recovered following ACV discontinuation and after a cycle of treatment with foscarnet. This isolate had lost the ACV-r trait and was characterized by a wild type TK sequence and by the production of a functional enzyme. Data presented confirm that a prolonged treatment with acyclovir can easily select ACV-r HSV-2 isolates carrying a TK- phenotype caused by a frameshift mutation. Although recovered from lesions tributary of different myelomers, these isolates may belong to the same strain that has undergone multiple cycles of reactivation and has possibly mutated during its axonal route to the skin.

[Latent cervical virus infection as a possible cause of early abortion]. / Latente zervikale Virusinfektion als mögliche Ursache des Frühaborts.

Cervical smears of 50 women who had an abortion were examined by dot-blot hybridization for human papillomavirus (HPV), herpes simplex virus (HSV) types 1 and 2, and cytomegalovirus (CMV) DNA. HPV DNA type 16 or 18 positivity was shown in 17.6% of the cases; in the aborted material, however, it amounted to 30.8%. IgM-positive titres were present in a few cases. In cervical smears of intact pregnancies, positivity for HPV DNA types 6 and 11 was detected in 9.5% and for the HSV DNA types 1 and 2 and CMV DNA in 48.0% of the cases. In this group of patients mostly positive IgM and IgG titers were present.

Comparison of immunocytochemistry and in situ hybridization in the cytodiagnosis of genital herpetic infection.

Over a 62-month period, 53 patients were found to have cervicovaginal smears that contained cells consistent with, or equivocal cells for, a herpes simplex virus (HSV) infection. The Papanicolaou-destained smears from these cases were restrained in situ hybridization (ISH) with a biotinylated cloned DNA probe and immunocytochemistry (ICC) assay and were compared for the detection of HSV in cervicovaginal smears by two methods. Cytological findings classified the 53 slides into two groups, i.e., cytologically herpes positive (33 patients) and equivocal cases (20 patients). Each group was subdivided into two groups: group A was confirmed by ICC, and group B was confirmed by ISH technique. Of the 33 cellular samples containing cells considered to be consistent with a herpes infection, 15 (88%) of 17 were positive by means of ICC technique (group A), 6 (43%) of 14 were positive by ISH technique (group B). Of the 20 smears showing equivocal cell changes thought unlikely to be caused by an HSV infection, 6 (60%) of 10 were positive by ICC (group A), 2 (29%) of 7 were positive by ISH (group B). With the ISH technique, five smears showed dislodged cells from glass slides due to enzyme treatment and denaturation. The results revealed that the ICC technique is a rapid and reliable procedure and thus recommended for routine diagnosis of HSV infection. Moreover, ICC is easier to perform and interpret and is less expensive than ISH. Therefore, the ICC may be preferable to ISH for detecting HSV in routine Papanicolaou diagnostic work.