彩色乳胶免疫层析法检测单纯疱疹病毒1,2型抗原临床应用分析

目的探讨彩色乳胶免疫层析法检测单纯疱疹病毒(HSV)1和2型抗原的临床应用价值。方法采用彩色乳胶颗粒免疫层析法检测各种水疱、溃疡和其他皮损中的HSV-1和2型抗原,同时用实时荧光定量PCR法进行对照。结果免疫层析法可检出≥1×106DNA拷贝/mL的HSV-1型混悬液和≥5×105DNA拷贝/mL的HSV-2型混悬液。132例标本中,免疫层析法检出HSV阳性43例,PCR检出HSV阳性50例。以PCR法为金标准,免疫层析法的灵敏度、特异度、阳性预测值和阴性预测值分别为84.00%,98.78%,97.67%和91.01%。结论免疫层析法检测HSV敏感性和特异性高,具有方便、快速和经济的特点,适于有症状患者的及时检测,对疱疹感染早期诊断和及时治疗有重要作用。     

Efficacy of cidofovir in an HIV infected patient with an acyclovir and foscarnet resistant herpes simplex virus infection]

BACKGROUND: We report the case of an AIDS patient, whose persistant HSV2 ulceration was clinically and phenotypically resistant to acyclovir and foscarnet. Only five clinical isolates of simultaneous acyclovir and foscarnet resistance have been previously described. CASE REPORT: This patient, without history of opportunistic infection, was hospitalized for a recurrent scrotal ulceration resistant to several antiviral treatment such as acyclovir, valacyclovir or foscarnet. The CD4 count was stable at 150/mm(3) and the HIV viral load was below detection level. The last recurrence appeared rapidly under valacyclovir therapy which had been introduced after 65 days of foscarnet therapy. Thus, the patient received a new dose of foscarnet. After initial efficacy, the ulceration increased once again. HSV2 phenotypic determination was done and detected, at that time, a double resistance to acyclovir and foscarnet. Healing was obtained with intravenous cidofovir. DISCUSSION: Foscarnet and acyclovir resistance in an HSV2 isolate is rare. This report presents several particularities. First, whereas the earlier published patients with an acyclovir and foscarnet resistant strain were widely immunocompromised, this was not the case for our patient. Secondly, in contrast with most precedent observations in which acyclovir-resistant strain disappeared after foscarnet therapy, in our case the acyclovir resistant strain remained after foscarnet therapy. Finally, few reports concerned the clinical efficacy of cidofovir in HSV infection. In this case, we proved that intravenously cidofovir was highly and rapidly effective on acyclovir and foscarnet resistant strains.     

生殖器部位皮损的单纯疱疹病毒检测及分型

目的 探讨生殖器疱疹部位皮损的不典型表现及其与单纯疱疹病毒型别的关系。方法 对外生殖器部位及其周围有硬结或疖肿、裂隙、毛囊炎等非水疱性皮肤黏膜损害的患者进行临床资料采集和分析,并对皮损标本进行单纯疱疹病毒的分离培养、PCR检测和病毒分型。结果 105例有外生殖器部位非水疱性皮损的患者入选本研究,在硬结(或疖肿)、裂隙、毛囊炎、类似擦破、单个溃疡、非特异性红斑和红肿渗液性包皮龟头炎皮损中,PCR检测HSV的阳性率分别33.3%(6/18)、20%(3/15)、37.5%(6/16)、28.6%(2/7)、33.3%(4/12)、20%(5/25)和50%(6/12),总的检出阳性率为30.5%(32/105)。分离培养法检测HSV的阳性率分别为22.2%(4/18)、13.3%(2/15)、25%(4/16)、14.3%(1/7)、33.3%(4/12)、8%(2/25)和41.7%(5/12),总的检出阳性率为21%(22/105)。两种方法检测HSV的总检出率差异无统计学意义(κ=0.095,P=0.114)。HSV-PCR分型结果与荧光单克隆抗体分型结果相符。在所有HSV阳性者中,HSV-1感染占9.4%(3/32),HSV-2感染占90.6%(29/32)。结论 生殖器HSV感染的皮肤黏膜损害多样,可为外生殖器部位的硬结(疖肿)、裂隙、毛囊炎、类似擦破、单个溃疡、非特异性红斑和红肿渗液性包皮龟头炎等不典型表现,而且主要由HSV-2感染引起。     

Seroprevalence of herpes simplex virus type 1 and type 2 in Turkey

BACKGROUND: Herpes simplex virus (HSV) infections are among the most common infectious diseases in humans. The prevalence of herpes simplex viruses type 1 (HSV-1) and type 2 (HSV-2) varies widely across the world. HSV-2 infection is the primary cause of genital herpes. It is highly prevalent in human populations in many parts of the world, and is the most common cause of genital ulcer disease worldwide. In spite of the large prevalence and growing incidence of herpes simplex infection (HSV-1 and HSV-2), relatively few data have been published regarding the seroprevalence of herpes simplex infection, while no data exist regarding the Turkish population. METHODS: We aimed to investigate the prevalence of HSV-1 and HSV-2 in selected populations in Turkey. A cross-sectional study was conducted involving 2082 serum samples of 725 adults, 300 pregnant women, 200 blood donors, 483 sex workers and 110 patients with genital warts and 264 hotel staff in Istanbul, Turkey. All serum samples were assessed for HSV1 and HSV-2 IgG antibodies using an HSV-type specific, enzyme-linked immunosorbent assay (ELISA). RESULTS: The prevalence of HSV-2 and HSV-1 antibodies was 4.8 and 85.3% in sexually active adults; 5.5 and 96% in blood donors; 5 and 98% in pregnant women, 17.3 and 93.6% in patients with genital warts; 8.3 and 97.3% in hotel staff; and 60% and 99% in sex workers. CONCLUSION: These results confirm a higher prevalence of HSV infection than estimated, especially in high risk groups in Turkey. The high prevalence of HSV infection underlines the need for education among these populations.     

Herpes simplex virus 2 infection in women attending an antenatal clinic in Fuzhou, China

Genital herpes caused by herpes simplex virus (HSV) infection is one of the most prevalent sexually transmitted infections (STIs) and the most common cause of genital ulcer disease (GUD) in developed and developing countries. The monitoring of HSV-2 seroprevalence in pregnant women can identify women at a higher risk of HIV and of neonatal HSV transmission. Very few data are available on type specific seroprevalence of HSV-2 in China, with only one previous study from southern China. Consequently, we conducted a survey to determine type specific seroprevalence of HSV-2 and associated risk factors in Fuzhou City, eastern China.     

Longitudinal study of herpes simplex virus type 2 infection using viral dynamic modelling

OBJECTIVES: Rates of reactivation of herpes simplex virus type 2 (HSV-2) change over time and these changes affect transmission and clinical management strategies. We conducted a longitudinal study of HSV-2 infection to quantify rates of change in HSV-2 reactivation, mucosal shedding and recurrences of genital lesions, using a newly available model of HSV within-host dynamics. METHODS: A cohort of 18 women was studied at two time periods spaced 2 years apart. The cohort provided daily mucosal swabs for HSV PCR analysis for 10 weeks during each time period and recorded recurrences in diaries. We fit the model of HSV dynamics to the mucosal shedding data using Bayesian methods to produce estimates of HSV reactivation, shedding and longitudinal rates of change. The model was validated using a separate group of 67 individuals. RESULTS: According to the viral dynamic modelling results, rates of HSV-2 reactivation from latency in the ganglia varied >10-fold among the women, and were estimated to be > or = 10% higher than rates of mucosal shedding episodes for many individuals. The mucosal shedding associated with each reactivation typically lasted 1-3 days. Reactivation frequency was estimated to be declining by three reactivations a year on average. The median number of recurrences, based on patient diaries, declined from 6.8 per year to 2.1 per year over the 2-year period. CONCLUSIONS: Rates of HSV-2 reactivation, shedding and recurrence generally decline over time but remain high in some individuals 4-5 years after primary infection. Viral dynamic modelling provides quantification of HSV infection that cannot be obtained by other methods.     

Chronic giant ulceration of the vulva in an HIV seropositive woman

Herpes simplex virus (HSV) infection is a common cause of genital ulceration. Primary presentation is usually with multiple, small, discrete, tender ulcers. We report an unusual case of chronic, giant ulceration of the vulva in a woman immunosuppressed by the human immunodeficiency virus (HIV). This was the first presentation of symptomatic disease. The diagnosis of HSV infection was made initially on histological examination of a punch biopsy from the ulcer and subsequently confirmed by viral isolation. The response to antiviral therapy with acyclovir was rapid. Other causes of genital ulceration are discussed and we highlight the diagnostic benefit of histological examination of a punch biopsy.     

Detection of varicella zoster virus in genital specimens using a multiplex polymerase chain reaction

OBJECTIVE: To compare the relative proportions of varicella zoster virus (VZV) and herpes simplex viruses in specimens obtained from the genital lesions of adults presenting with presumed genital herpes infection. METHODS: Swabs of genital lesions from 6210 patients attending general practices, infectious diseases clinics within hospitals, or sexual health centres for treatment of their genital lesions were tested using polymerase chain reaction (PCR) technology. The multiplexed PCR was capable of detecting herpes simplex virus types 1 and 2 (HSV-1, HSV-2), VZV, and cytomegalovirus in a single sample. RESULTS: A total of 2225 patients had viruses detected by PCR. HSV-1 was detected in 36%, HSV-2 in 61%, and VZV in 2.9% of PCR positive samples. Of the 65 patients with VZV genital infection, many were thought to have HSV infection before laboratory testing. CONCLUSIONS: The finding of VZV in nearly 3% of virus positive genital specimens demonstrates that this virus needs to be considered as a differential diagnosis for genital herpetic lesions. Advice provided to patients with VZV genital infection regarding the source of infection, likelihood of recurrence, and potential for transmission of the virus will be different from that given to patients with HSV infection.     

Herpes simplex virus infection and genital ulcer disease among patients with sexually transmitted infections in Dar es Salaam, Tanzania

The relative importance of Haemophilus ducreyi and Treponema pallidum in genital ulcer disease in Africa has decreased recently, whereas that of herpes simplex virus (HSV) type 2 has increased. We analysed 301 lesional specimens from Tanzanian patients with genital ulcer disease for the presence of H. ducreyi, T. pallidum and HSV-1/HSV-2 by performing a separate PCR for each pathogen. Infectious agents were detected in 211 (70%) of the cases. A single pathogen was found in 191 samples and two or more pathogens in the remaining 20. HSV-2 represented 83% of all identified pathogens, HSV-1 8%, T. pallidum 4% and H. ducreyi 5%. HSV-1 was identified as a single pathogen in four samples, in combination with others in an additional 14 samples. Thus, HSV-1 can also be the cause of genital ulcer disease in Africa. Regular surveillance of genital ulcer disease aetiology is important in programs for management of genital ulcer disease and HIV in Africa.     

An indolent penile herpetic ulcer in a patient with previously undiagnosed human immunodeficiency virus infection

We report a case of an atypical penile herpetic ulcer in a man with previously undiagnosed human immunodeficiency virus (HIV) infection. Swabs of the lesion were negative for herpes simplex virus (HSV) by culture and electron microscopy. However, histopathology of biopsy material showed characteristic herpetic multinucleate giant cells. Immunochemistry using polyclonal antibodies was positive for HSV1 and HSV2. The lesion completely resolved after treatment with aciclovir and the patient subsequently tested positively for HIV antibodies.     

宫颈糜烂患者单纯疱疹病毒Ⅱ型感染情况分析

目的探讨宫颈糜烂患者单纯疱疹病毒(HSV-Ⅱ)感染情况。方法用实时荧光定量PCR法对212例受试者宫颈棉拭子中HSV-Ⅱ进行检测。结果 162例宫颈糜烂患者中,HSV-Ⅱ阳性率为29.01%(47/162),50例正常对照组中,HSV-Ⅱ阳性率为10.00%(5/50),两组差异有统计学意义(P<0.05)。Ⅰ,Ⅱ和Ⅲ度宫颈糜烂患者HSV-Ⅱ阳性率分别为19.64%(11/56),27.78%(15/54)和40.38%(21/52),提示宫颈糜烂程度与HSV-Ⅱ的阳性率呈正相关(r=0.186,P<0.05)。结论 HSV-Ⅱ感染与宫颈糜烂密切相关,且随宫颈糜烂程度的增加,HSV-Ⅱ感染率增加。应加强对宫颈糜烂患者HSV-Ⅱ的检测。     

Increasing relative prevalence of HSV-2 infection among men with genital ulcers from a mining community in South Africa

OBJECTIVES: To determine the aetiology of genital ulcer disease (GUD) and its association with HIV infection in the mining community of Carletonville, South Africa, from two cross sectional surveys of consecutive men presenting with genital lesions during October 1993 to January 1994 and July to November 1998. METHODS: A multiplex polymerase chain reaction (M-PCR) assay combined with amplicon detection was used to identify DNA specific sequences of Treponema pallidum, herpes simplex virus (HSV), and Haemophilus ducreyi. A real time PCR assay was used to differentiate between HSV-1 and HSV-2. RESULTS: M-PCR detected T pallidum, HSV, and H ducreyi in 10.3%, 17.2%, and 69.4% of 232 GUD patients during 1993-4 and in 12.4%, 36.0%, and 50.5% of 186 GUD patients in 1998. The proportion of patients with more than one agent increased significantly from 7.3% (17/232) in 1993-4 to 16.7% (31/186) in 1998 (p <0.01). HSV-2 was detected in a higher proportion of ulcer specimens from HIV infected patients than in specimens from HIV uninfected patients during both time periods (1993-4: 26.2% v 6.7%, p <0.001; 1998: 42.1% v 29.6%, p >0.09). CONCLUSIONS: Based on two cross sectional surveys, 4 years apart, chancroid remained the leading cause of GUD in men who presented at the STD clinic with genital ulcers in the mining community of Carletonville, South Africa. The relative prevalence of primary syphilis has remained low. However, HSV-2 has emerged as a more significant cause of GUD and the proportion of GUD patients infected with more than one agent also increased significantly. HSV-2 DNA was detected in a significantly higher proportion of ulcer specimens from HIV positive patients than from HIV negative patients. No association was found between HIV infection status and the relative prevalence of chancroid or syphilis.     

Chronic herpes simplex virus type I glossitis in an immunocompromised man

Herpes simplex virus (HSV) type 1 (HSV-1) infection of the tongue commonly accompanies acute primary herpetic gingivostomatitis. However, recurrent infection of the tongue is exceptional and is restricted to immunocompromised individuals. A 57-year-old man with corticosteroid-dependent chronic obstructive pulmonary disease and sciatica presented with a chronic median glossitis due to HSV-1. The main clinical and histological feature was massive necrosis of the entire mucosa. Immunohistochemistry demonstrated a considerable amount of HSV gB, gC and gD envelope glycoproteins dispersed in the chorion. In contrast, HSV-1 DNA was detected only in a limited number of epithelial cells using in situ hybridization. The extent of necrosis and the pattern of viral DNA and envelope protein distribution represent unique features of median herpetic glossitis, which are not found in more common types of HSV infection.     

Nodular perianal herpes simplex with prominent plasma cell infiltration

BACKGROUND: Nodules are exceptional manifestations of herpes simplex virus (HSV) infection in immunocompromised patients. Only two cases of nodular HSV-2 infection of the perianal region have been reported previously. GOAL: The case of a 46-year-old homosexual man with AIDS presenting with painful perianal nodules resembling squamous cell carcinoma is described. STUDY DESIGN: This case report presents details of the histologic findings and treatment regimen. RESULTS: Histologic examination showed the presence of rare multinucleated giant epithelial cells and a dense inflammatory infiltrate composed mostly of plasma cells. Polymerase chain reaction analysis was positive for HSV-2 and negative for HSV-1, cytomegalovirus, Epstein-Barr virus, and human herpesvirus types 6 and 7. After being treated ineffectively with oral acyclovir (4 g/d) for 15 days, the patient was treated with oral valacyclovir (6 g/d), resulting in marked improvement in 10 days and complete resolution after 2 months. CONCLUSIONS: In immunocompromised patients, HSV-2 infection may present with atypical clinical and histopathological features.     

Topical imiquimod treatment of aciclovir-resistant herpes simplex disease: case series and literature review

Infection with herpes simplex virus (HSV) is extremely common worldwide. In immunocompromised patients anogenital HSV disease may have atypical features and may be very severe. Treatment of aciclovir-resistant anogenital HSV disease is challenging, as resistance to alternative treatments may occur, and effective treatment generally involves intravenous therapy with relatively toxic agents such as foscarnet. This case report presents three immunocompromised patients with presumed aciclovir-resistant anogenital HSV disease who were successfully treated with topical imiquimod. Imiquimod promotes local immune activation, which results in resolution of viral lesions such as anogenital warts and HSV disease. It is convenient to use and avoids the necessity for intravenous treatment with substantial systemic toxicity. In addition, as the mode of action of imiquimod is related to immune stimulation rather than direct antiviral activity, it may be used repeatedly without resistance developing.     

Atypical severe progressive perioral ulceration due to herpes simplex virus on the background of undiagnosed HIV/AIDS

Perioral ulcerative plaques have a broad list of differential diagnoses. We describe an unusual presentation of chronic progressive perioral ulceration due to herpes simplex type (HSV)-1 on a background of undiagnosed human immunodeficiency virus infection with acquired immunodeficiency syndrome. Whilst chronic mucocutaneous HSV is an AIDS-defining condition with both HSV-1 and HSV-2 implicated, typical reported cases describe vesicular eruptions rather than perioral ulcerative plaques. This case highlights that common infections may present atypically in immunocompromised individuals and may be a clue to underlying systemic illness.     

Sequential genital infections by herpes simplex viruses types 1 and 2: restriction nuclease analyses of viruses from recurrent infections

Virus isolated from a woman presenting with the first symptomatic episode of genital herpes was identified as herpes simplex virus type 1 (HSV-1) by restriction nuclease fingerprinting. Testing for IgM antibody to HSV indicated that the patient had recently contracted a new HSV infection. Virus microneutralization and the micro-solid phase radioimmunometric test for IgG, however, showed that the patient had had prior infection with herpes simplex virus type 2 (HSV-2); thus the HSV-1 infection was acquired despite the presence of antibody to HSV-2. Genital herpes recurred about four, seven, and nine months after the HSV-1 infection. Isolates from the latter three episodes all were of an identical strain of HSV-2 and were not recombinants or a mixture of the viruses. The data show that two distinctly different herpes simplex viruses can initiate genital infections in one individual and suggest that HSV-2 is more likely to recur than HSV-1.     

Coexistent infections on a child's distal phalanx: blistering dactylitis and herpetic whitlow

We report a case of coexistent Staphylococcus aureus and herpes simplex virus (HSV) infections responsible for a bullous and vesicular eruption on a child's distal phalanx. Blistering distal dactylitis (BDD), a superficial infection of the distal portion of the finger, is seen most commonly in children and is caused by either beta-hemolytic streptococci or S aureus. Herpetic whitlow, also a blistering infection found on children's distal fingers, is a bacteriologic sterile infection caused by HSV-1 or HSV-2. In this report, we note that these infections may coexist on the distal phalanx. This case has implications for diagnosis and treatment of children's blistering hand diseases.     

婴幼儿疱疹性瘭疽1例

报告1例婴幼儿疱疹性瘭疽。患儿男,1岁,左手中指甲周红斑伴肿胀1周余。皮肤科检查：左手中指远端水疱形成,其内少许透亮疱液、甲周红斑。皮损处疱液单纯疱疹病毒-1型(HSV-1)聚合酶链反应阳性。结合临床、实验室检查结果诊断为疱疹性瘭疽。未予特殊处理,随访10 d,皮损自行消退。3个月后门诊随访未见复发。     

Extensive oral condylomas treated by in situ cidofovir injection in an HIV patient

BACKGROUND: Human papillomavirus infections are difficult to treat and have a high rate of recurrence, especially in a setting of human immunodeficiency (HIV) infection. Moreover, there is no standard treatment for oral condylomas. PATIENTS AND METHODS: We report the partial success of in situ injections of cidofovir in an HIV patient, presenting extensive oral condylomas. The injections were well tolerated and the response was still present at one year while the immune status of the patient was unchanged. DISCUSSION: The efficacy of topical cidofovir against condyloma acuminata has been reported and the value of in situ cidofovir injections for the treatment of laryngeal papillomatosis is well established. This case report shows the need for further investigation of in situ cidofovir injections as an alternative treatment for human papillomavirus lesions that are difficult to treat because of both site and extension.