Molecular methods for the diagnosis of genital ulcer disease in a sexually transmitted disease clinic population in northern Thailand: predominance of herpes simplex virus infection

A multiplex polymerase chain reaction (M-PCR) assay that simultaneously detects the three major causes of genital ulcer disease (GUD), Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus, was used to evaluate swab specimens for 38 sequential patients with GUD at a Thai sexually transmitted disease clinic. Subjects received clinical diagnoses and syndromic treatment. Swab specimens for H. ducreyi cultures and M-PCR were obtained. No H. ducreyi cultures were positive. Of 38 M-PCR specimens, 31 (81.6%) were positive for HSV, 1 (2.3%) for both HSV and T. pallidum, and none for H. ducreyi or T. pallidum alone; 6 (15.8%) were negative for all 3 pathogens. Clinical diagnoses corresponded poorly to M-PCR findings; none of 5 suspected cases of chancroid were positive by M-PCR and none of 1 for syphilis, but 21 of 24 suspected herpes lesions were confirmed by M-PCR. Human immunodeficiency virus infection status was known for 24 of 38 subjects; 11 (45.8%) were seropositive, and all 11 had HSV by M-PCR. HSV appeared to be the most common pathogen overall.     

Etiology of genital ulcers and prevalence of human immunodeficiency virus coinfection in 10 US cities. The Genital Ulcer Disease Surveillance Group

To determine the etiology of genital ulcers and to assess the prevalence of human immunodeficiency virus (HIV) infection in ulcer patients in 10 US cities, ulcer and serum specimens were collected from approximately 50 ulcer patients at a sexually transmitted disease clinic in each city. Ulcer specimens were tested using a multiplex polymerase chain reaction assay to detect Haemophilus ducreyi, Treponema pallidum, and herpes simplex virus (HSV); sera were tested for antibody to HIV. H. ducreyi was detected in ulcer specimens from patients in Memphis (20% of specimens) and Chicago (12%). T. pallidum was detected in ulcer specimens from every city except Los Angeles (median, 9% of specimens; range, 0%-46%). HSV was detected in >/=50% of specimens from all cities except Memphis (42%). HIV seroprevalence in ulcer patients was 6% (range by city, 0%-18%). These data suggest that chancroid is prevalent in some US cities and that persons with genital ulcers should be a focus of HIV prevention activities.     

Comparison of enzyme immunoassays for antibodies to Haemophilus ducreyi in a community outbreak of chancroid in the United States

The performance of two EIAs (adsorption EIA and lipooligosaccharide [LOS] EIA) that detect antibodies to Haemophilus ducreyi was evaluated with serum specimens obtained from 163 patients (96 with genital ulcer disease [GUD]). Paired serum specimens (initial and follow-up) were obtained from 52 of the GUD patients. By use of initial serum specimens from 82 GUD patients whose etiologic agents for their ulcers had been identified, the adsorption EIA had a sensitivity and specificity for chancroid of 53% and 71%, while the LOS EIA had a sensitivity and specificity of 48% and 89%, respectively. Sensitivity and specificity of the adsorption EIA increased to 78% and 84%, respectively, when the results of follow-up serum specimens were used to calculate optimal performance. The proportion of patients testing positive for H. ducreyi who had anti-H. ducreyi IgG antibodies, as determined by adsorption EIA, increased with the duration of infection, thus limiting the role of EIAs in the diagnosis of chancroid.     

Prevalence of herpes simplex virus type 1- and 2- specific antibodies among the acute, recurrent, and provoked types of female genital herpes

Sixty-eight sera from the acute, recurrent, and provoked types of female genital herpes were compared for the seroprevalence of herpes simplex virus (HSV) types 1 and 2 by immunodot assay using HSV glycoprotein G. In the HSV-1-isolated patients, no HSV-2 antibodies were detected, whereas in the HSV-2-isolated patients, HSV-1 seroprevalence was 9% for the acute type, 89% for the provoked type (P < 0.005), and 55% for the recurrent type (P < 0.05). The natural history of female genital herpes and the possible protective role of pre-existing antibodies in preventing the acquisition or clinical manifestation of a subsequent HSV infection are discussed.     

Oral famciclovir for the suppression of recurrent genital herpes: a randomized controlled trial. Collaborative Famciclovir Genital Herpes Research Group

CONTEXT: Recurrent genital herpes simplex virus (HSV) may be treated episodically, but this may not be sufficient for patients with frequent recurrences. OBJECTIVE: To determine the efficacy and safety of famciclovir in the suppression of recurrent genital HSV infection. DESIGN: A randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Thirty university, hospital, or private outpatient referral centers in Canada and Europe. PATIENTS: A total of 455 patients (223 men, 232 women) aged 18 years or older with a history of 6 or more episodes of genital herpes during 12 of the most recent 24 months, in the absence of suppressive therapy, received study medication. INTERVENTION: Oral famciclovir, 125 mg or 250 mg 3 times daily or 250 mg twice daily, or placebo for 52 weeks. MAIN OUTCOME MEASURES: Time to the first recurrence of genital HSV infection; the proportion of patients remaining free of HSV recurrence at 6 months; frequency of adverse events. RESULTS: In an intent-to-treat analysis, famciclovir significantly delayed the time to the first recurrence of genital herpes at all dose regimens (hazard ratios, 2.9-3.3; P<.001); median time to recurrence for famciclovir recipients was 222 to 336 days compared with 47 days for placebo recipients. The proportion of patients remaining free of HSV recurrence was approximately 3 times higher in famciclovir recipients (79%-86%) than in placebo recipients (27%) at 6 months (relative risks, 2.9-3.1; P<.001); efficacy was maintained at 12 months. Famciclovir was well tolerated with an adverse experience profile comparable to placebo. CONCLUSIONS: Oral famciclovir (125 mg or 250 mg 3 times daily or 250 mg twice daily) is an effective, well-tolerated treatment for the suppression of genital HSV infection in patients with frequent recurrences.     

Genital herpes. Type-specific antibodies for diagnosis and management

The high incidence of unrecognized genital herpes infections and the role of such undiagnosed infections in continuing the spread of genital herpes has been due, in part, to the limited availability of accurate serologic assays for herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Type-specific serology test kits for HSV diagnosis have been developed and are expected to be widely available in 1998. Clinicians should understand the proper application of these new test and in addition, should be aware that older, inaccurate test will remain on the market for the foreseeable future.     

Consequences of the latest Euratom directive 96/29 ("basic standard") regarding radiotherapy]

BACKGROUND AND OBJECTIVES: To determine the prevalence rates of serological reactivity of Haemophilus (H.) ducreyi, Treponema pallidum, and herpes simplex virus type 2 (HSV-2) antibodies among female sex workers (FSWs) and their association with human immunodeficiency virus (HIV) antibody status. STUDY DESIGN: Cross-sectional, standard serological assays were used for syphilis, HSV-2 and HIV; a modified enzyme-linked immunosorbent assay (ELISA) was used to detect specific anti-H. ducreyi immunoglobulin (Ig) G and IgA antibodies. RESULTS: Seroprevalence rates were 86% for anti-H. ducreyi IgG and 69% for anti-H. ducreyi IgA; 4% for rapid plasma reagin (RPR) and Treponema palladium hemagglutination assay (TPHA) confirmed syphilis; 59% for HSV-2; 12% for HIV-1 and 2% for HIV-2. Lower-class FSWs were significantly more likely than upper-class FSWs to be H. ducreyi seropositive (IgG: OR = 42.7; IgA: OR = 7.6) and have current or past syphilis infection (RPR: OR = 3.5; RPR and TPHA: OR = 4.5). The presence of syphilis increased significantly with older age (P-trend < 0.001). Non-Nigerian FSWs had significantly higher reactivity to chancroid (IgG: OR = 3.5; IgA: OR = 1.8) and borderline reactivity to syphilis (RPR: OR = 1.6; TPHA: OR = 2.0). A history of sex with non-Nigerian Africans was significantly associated with chancroid reactivity and borderline significant with syphilis serostatus. H. ducreyi seropositivity was significantly more likely in FSWs with HSV-2 (OR = 2.4) and syphilis (OR = 5.6). Chancroid and HSV-2 antibodies were also more common in HIV-infected FSWs. CONCLUSION: The prevalence of H. ducreyi antibodies is the highest rate that has been reported. Our findings underscore the importance of an effective program to control GUDs as part of the strategy to prevent the potentially explosive spread of HIV in Nigeria.     

Evidence of latency and reactivation of both herpes simplex virus (HSV)-1 and HSV-2 in the genital region

While superinfection with different herpes simplex virus (HSV) types has been demonstrated in animals, the ability of the two HSV types to colonize and reactivate in the same anatomic region in humans has not been well demonstrated. In 6 patients, both HSV-1 and HSV-2 was recovered from genital lesions. In 4 of them, who initially acquired genital HSV-1 infection, subsequent HSV-2 infection presented as a prolonged episode of genital lesions and a marked increase in the frequency of genital recurrences. While most of the subsequent clinical reactivations were HSV-2, in 2 patients the recurrence rate of genital HSV-1 increased after the acquisition of HSV-2. These data demonstrate the ability of a second HSV type to infect the same anatomic region and illustrate the difference in reactivation frequency of the two types in the same person. Typing of HSV isolates may be useful in persons with recent alteration in recurrence rates of genital HSV.     

Polymerase chain reaction-based assays of vitreous samples for the diagnosis of viral retinitis. Use in diagnostic dilemmas

OBJECTIVE: This study aimed to review the authors' results using polymerase chain reaction (PCR)-based assays for the diagnosis of viral retinitis. DESIGN: The study design was a retrospective case series. PARTICIPANTS: Thirty-seven patients (38 eyes) with active retinitis from whom vitreous biopsy specimens were received in the authors' laboratory for diagnostic evaluation. INTERVENTION: Vitreous biopsy specimens were evaluated with previously described PCR-based assays for cytomegalovirus (CMV), varicella zoster virus (VZV), and herpes simplex virus (HSV) DNA; clinical histories were reviewed. MAIN OUTCOME MEASURES: Laboratory findings and clinical course were measured. RESULTS: The results of the authors' assays were consistent with the long-term clinical course of each patient. Cytomegalovirus, VZV, or HSV DNA was detected in the vitreous from 24 patients. Cytomegalovirus DNA was detected in vitreous biopsy specimens from 10 patients (11 eyes). Nine patients (ten eyes) with acquired immune deficiency syndrome ultimately were diagnosed with CMV retinitis as they were followed clinically over time. Varicella zoster virus DNA was detected in vitreous biopsy specimens from eight patients; seven adult patients were ultimately diagnosed with acute retinal necrosis or progressive outer retinal necrosis. Herpes simplex virus DNA was detected in vitreous biopsy specimens from six patients; five patients had previous or subsequent herpes encephalitis. No viral DNA was detected in the vitreous from 13 patients; all were ultimately diagnosed with toxoplasmosis, syphilis, Behcet disease, fungal endophthalmitis, or idiopathic inflammation. CONCLUSIONS: These data further support the use of PCR-based assays of vitreous specimens in the diagnostic evaluation of patients with infectious retinitis.     

Morning-to-evening change in refraction, corneal curvature, and visual acuity 11 years after radial keratotomy in the prospective evaluation of radial keratotomy study. The PERK Study Group

One-hundred thirteen men (mean age, 23 years) who presented with inguinal buboes to a government-operated hospital for sexually transmitted diseases (STDs) in Bangkok were studied between February 1987 and February 1989. The median duration of preceding symptoms was 7 days (range, 1-62 days). The majority of patients (74; 65%) had received treatment previously; 31 (27%) were febrile, 13 (12%) had extrainguinal lymphadenopathy, and 31 (27%) had concurrent active genital ulcers. There was no history of genital ulceration in 66 (58%) of the patients. Pus was obtained from 51 of the 110 buboes aspirated for culture; 21 (41%) of these cultures yielded Haemophilus ducreyi, and 2 (3.9%) were positive for Chlamydia trachomatis on immunofluorescence microscopy. Saline (1 mL) was injected and reaspirated from the buboes of 35 of the other 59 patients; 3 buboes yielded H. ducreyi and 9 were positive for C. trachomatis. All cultures for other aerobic and anaerobic bacteria and viruses in intact buboes were negative. Syphilis serology was positive in only one case. Patients attending STD clinics in this region who have large, fluctuant, edematous inguinal buboes containing pus should receive presumptive treatment for chancroid. If there is no pus, then the bubo is more likely to be caused by lymphogranuloma venereum.     

The relationship among genital herpes simplex virus, stress, and social support.

Examined the role of stress in activation of genital herpes simplex virus (HSV) lesions, as mediated by social support, in 59 adults who had self-reported culture-positive genital HSV for at least 10 mo. Retrospective reports of HSV symptoms revealed that duration of disease and herpes-specific social support were significant moderators of the relation between stress and number of HSV recurrences (HSV-R) in the preceding 12 mo. When duration of disease was short (     

Herpetic esophagitis in 5 immunocompetent patients

In five immunocompetent patients, 3 of whom were moderately ill, herpes simplex virus (HSV) oesophagitis was diagnosed. HSV oesophagitis is a frequent infection in immunocompromised hosts. Nevertheless the English medical literature (Medline) contains at least 33 cases of HSV oesophagitis in immunocompetent persons over the period 1983 to 1993. Odynophagia, dysphagia and chest pain are common symptoms. Endoscopy is necessary for diagnosis: brush cytology, biopsy for histology and viral culture are the tools for identification of herpes simplex as the cause of the oesophagitis. HSV oesophagitis in an immunocompetent patient is an acute but self-limiting disease. Nevertheless acyclovir per os or intravenously may be recommended if started early after onset of symptoms.     

Herpes. Atypical clinical manifestations

Herpes simplex viruses (HSV) 1 and 2 are responsible for genital herpes which is usually recognized as vesicles that ulcerate and eventually heal but recur periodically. Atypical genital herpes is often described in immunocompromised patients and can present as large, chronic, hyperkeratotic ulcers. Acyclovir-resistant HSV is occasionally isolated from such ulcers. Most cases of HSV infection reproduce subtle signs and symptoms, or more commonly, asymptomatic viral shedding. Such subclinical presentations may be responsible for most of the 30% increase in the prevalence of genital herpes in the United States during the past two decades.     

Subcutaneous implantation metastasis of a cholangiocarcinoma of the bile duct after percutaneous transhepatic biliary drainage (PTBD)

The differential diagnosis of herpes simplex and zoster may require virological confirmation, yet virus typing is not regarded as necessary in routine dermatological assessment. In an attempt to evaluate the clinical benefits of the routine detection of herpes simplex virus (HSV) and varicella zoster virus (VZV), we analysed skin swabs from 110 patients who were diagnosed at the first clinical visit as having herpes simplex (n = 45) or zoster (n = 65). Viruses were typed using the polymerase chain reaction (PCR) with the general primer pair GPHV-RU. PCR analysis showed that at the initial clinical presentation, herpes simplex in these patients was not mistaken for zoster but that zoster was incorrectly diagnosed as herpes simplex in nine cases. Thus these results suggest that initial zoster often mimics herpes simplex, hence routine PCR diagnosis of HSV and VZV or alternative rapid diagnostic approaches may be beneficial in these cases.     

Severe myelotoxicity of oral etoposide in heavily pretreated patients with non-Hodgkin''s lymphoma or chronic lymphatic leukemia

In this study we aimed to determine the incidence of herpes simplex virus (HSV) in the lungs of burns patients, and its association with the presence of adult respiratory distress syndrome (ARDS) and pneumonia. Haematoxylin and eosin (H&E), and immunohistochemical (IHC) staining for HSV was performed on lung tissue from 54 patients who had died following burn injury and from nine control cases. Polymerase chain reaction (PCR) for HSV deoxyribonucleic acid (DNA) was performed on a subset both of burns cases and controls. No viral inclusions were detected in H&E sections, but 50% of the burns cases were positive for HSV by IHC staining; no control cases were positive. Nuclear and cytoplasmic immunopositivity for HSV was seen in macrophages and epithelial lining cells. HSV was strongly associated with ARDS (p=0.007), but not with pneumonia (p=0.577). The relative risk of HSV infection was higher for cases with ARDS (2.21) than for those with pneumonia (1.26). PCR for HSV DNA was positive in three out of five burns cases, and in one out of five control cases. Immunohistochemical staining is more sensitive for the detection of herpes simplex virus than haematoxylin and eosin staining for detection of viral inclusions. Burns cases have a high incidence of pulmonary herpes simplex virus infection. Polymerase chain reaction results may not be fully representative due to problems of tissue necrosis postmortem. Pulmonary herpes simplex virus is strongly associated with adult respiratory distress syndrome and the two may be causally linked. Early detection and treatment of pulmonary herpes simplex virus in burns patients may reduce pulmonary complications and mortality.     

Unexpected correlation in the sensitivity of 19 herpes simplex virus strains to types I and II interferons

We compared the sensitivity of 19 herpes simplex virus (HSV) strains to type I (IFN-alpha and IFN-beta) and type II (IFN-gamma) human interferons in cultures of human retinal epithelial (K-1034) and lung (HEL) cells. Their sensitivities proved to be well correlated, even though type I and type II IFN have been reported to have different antiviral actions. The correlation was not because IFN-gamma stimulated the formation of IFN-beta, for an antibody that neutralized IFN-beta did not reduce its inhibitory effects. Our results show that each HSV strain has a characteristic and similar sensitivity to type I and type II IFN and suggest some common pathway in the mechanism of their antiviral actions.     

Recovery of cytomegalovirus and herpes simplex virus from upper and lower genital tract specimens obtained from women with pelvic inflammatory disease

Lower genital tract specimens and endometrial biopsies from 147 women with pelvic inflammatory disease (PID) and surgical specimens (fallopian tubes, ovaries, or both) from 22 women with PID and 37 women without PID were cultured for cytomegalovirus (CMV) and herpes simplex virus (HSV), as well as for organisms commonly associated with PID. CMV was isolated from 39 cervical or endometrial samples from 30 (20.4%) of 147 women with PID and from ovaries or fallopian tubes from 5 (22.7%) of 22 women with PID, but CMV was not recovered from surgical specimens obtained from 37 women undergoing surgery for tubal ligation, ectopic pregnancy, or other gynecologic conditions (P = .005). HSV was isolated from cervical samples obtained from 5 (3.4%) of 147 women with PID but not from any endometrial or surgical specimens. These data suggest that CMV, but not HSV, may contribute to the pathogenesis of PID in some patients.     

The causal role for genital ulcer disease as a risk factor for transmission of human immunodeficiency virus. An application of the Bradford Hill criteria

BACKGROUND AND OBJECTIVES: Genital ulcer disease (GUD) has been reported to increase the risk for the acquisition of human immunodeficiency virus (HIV). Although many investigators have reported an increased risk for HIV infection in persons with concurrent or previous GUD, not all studies have been designed to determine whether GUD causes an increased risk for HIV infection or acts only as a risk marker for infection. The evidence from the literature is discussed, and the criteria for causal inference proposed by Sir Austin Bradford Hill are applied. GOAL: To evaluate the strength of the association between GUD and infection by HIV. STUDY DESIGN: Case-control, cross-sectional, and cohort studies that examined the association between HIV seroconversion and GUD were chosen from the literature. Twenty-seven epidemiologic studies were selected for analysis, many of which reported separate analyses of the association between HIV infection and herpes simplex virus infection, syphilis, or nonspecified GUD. The studies were analyzed to investigate the magnitude of association between GUD and HIV, and the evidence evaluated using Hill's criteria. RESULTS: Approximately two thirds of the analyses reported a statistically significant association between GUD and HIV infection. Fourteen studies reported 29 separate analyses using a case-control design, 18 of which reported a statistically significant association between GUD (GUD, herpes, and syphilis) and HIV infection, four analyses were of varying significance depending on the analytical technique used, and seven were nonsignificant. Thirteen studies reported 23 separate longitudinal analyses that used a nested case-control or cohort design: 11 reported a significant association, 11 had nonsignificant findings, and results of one study varied. No study reported a statistically significant negative association. When applying the literature to Hill's criteria, all nine criteria for causal inference were met, providing additional evidence that genital ulcers are associated with an increased risk for the development of HIV infection. CONCLUSIONS: The published evidence suggests that GUD increases the risk for HIV acquisition. Few studies, however, have examined carefully the temporal association between preexisting GUD and subsequent HIV acquisition. The analyses that simultaneously controlled for additional risks for HIV infection, such as lifetime sex partners or history of injection drug use, report a generally lower risk for HIV associated with GUD. It is likely that studies that adequately control for risk factors will find a lower risk associated with GUD than was reported in the literature earlier in the HIV epidemic. Future research needs and the problems associated with conducting these types of studies are discussed.     

The prophylactic effect of immunization with DNA encoding herpes simplex virus glycoproteins on HSV-induced disease in guinea pigs

Plasmid expression vectors encoding herpes simplex virus type 2 (HSV-2) glycoproteins B (gB) or D (gD) were constructed and tested for their ability to immunize guinea pigs against genital HSV infection. Immunization with a plasmid expressing the aminoterminal 707 amino acids (aa) of gB induced humoral immune responses detected by ELISA and virus neutralization. When challenged by vaginal infection, immunized animals were partially protected from genital herpes, exhibiting significantly reduced primary and subsequent recurrent disease. When the gB plasmid was combined with a plasmid expressing full-length gD, immunized guinea pigs developed humoral responses to both proteins and were also significantly protected from viral challenge.