Type-specific herpes simplex virus-1 and herpes simplex virus-2 seroprevalence in Romania: comparison of prevalence and risk factors in women and men.

OBJECTIVE: To determine herpes simplex virus (HSV)-2 and HSV-1 seroprevalence in women and men in Romania. METHODS: A cross-sectional seroprevalence survey was conducted between 2004 and 2005 on a total of 1058 women and men representative of the population of Bucharest. All participants were aged 15-44 years and completed a structured questionnaire. A blood sample was collected to detect IgG anti-HSV-1 and HSV-2 serum antibodies using the HerpeSelect ELISA (Focus Diagnostics). RESULTS: A total of 761 women (median age 29 years) and 297 men (median age 29 years) were included. Overall, HSV-2 seroprevalence (15.2%) increased with age. Among women, HSV-2 seroprevalence increased from 11.0% in 15-19-year-olds to 38.3% in 40-44-year-olds. Among men, seroprevalence increased from 4.0% in 20-24-year-olds to 27.1% in 40-44-year-olds. HSV-2 seroprevalence was significantly higher among women than men (17.0% vs. 10.8%). HSV-1 seropositivity was high (87.2%) in all age groups, with no clear trend by age or by sex. In addition to older age and female sex, risk factors for HSV-2 included greater number of lifetime sexual partners, lower educational attainment, and history of genital vesicles. Lower educational level and rural residence were associated with a higher risk of HSV-1 seropositivity. CONCLUSIONS: In Romania, HSV-2 seroprevalence was higher in women than men, and was within European limits and lower than that in Africa and the USA. In contrast, HSV-1 seroprevalence was generally higher than that previously recorded in similarly aged populations in Western Europe.

Epidemiology of orofacial herpes simplex virus infections in the general population in France: results of the HERPIMAX study.

BACKGROUND: Prevalence of clinically manifest orofacial herpes in the general population is poorly characterized. Objectives To establish the lifetime prevalence of clinically manifest orofacial herpes and its relationship with herpes simplex virus (HSV) serotype in the French general population. PATIENTS/METHODS: Subjects (N = 2796) were serotyped for HSV1 and HSV2 and provided data on herpetic symptoms by questionnaire. Subjects reporting at least one episode of orobuccal ulcerative mucosal lesions were classified as clinically manifest orofacial herpes. RESULTS: Lifetime prevalence of clinically manifest orofacial herpes was 38.3% (42.1% in women, 32.4% in men). Prevalence in subjects seropositive for HSV1 was 50.3%. This prevalence rate was independent of HSV2 serotype. Prevalence in subjects infected with HSV2 alone was similar to that in subjects seronegative for HSV. LIMITATIONS: Lack of case ascertainment limits precision of the data. CONCLUSIONS: Clinically manifest orofacial herpes was reported in one third of the sample, principally associated with HSV1 infection. HSV2 infection did not produce orofacial lesions nor influence clinical manifestations of HSV1 infection.

[Assessment of a programme of prevention of mother-to-child transmission of HIV in Abidjan, Ivory Coast (1999-20002)]. / Evaluation d'un programme de prévention de la transmission mère- enfant ou VIH à Abidjan (Côte d'Ivoire/1999-2002).

The purpose of this article is to report the results of a programme for prevention of mother-to-child transmission (PMCT) of HIV conducted from 1999 to 2002 by the PNLS in Abidjan, Ivory Coast. This programme was supported by grants from the Fonds de solidarité international (FSTI) and the Glaxo Smith Kline (GSK) Foundation. After pre- and posttest counselling, pregnant women from 4 PMI centres underwent screening for HIV. Seropositive women were offered short course AZT and the possibility of financial assistance for breast-feeding. All programme activities were carried out in close cooperation with association members. A total of 22466 tests were given and 18116 women returned for results. Among the 1829 seropositive women to whom PMCT intervention was proposed, 667 received short course AZT. The rate of transmission at 18 months was 162%. In addition 69 mothers and 28 children eligible for ARV therapy benefited from tritherapy. Limiting factors, at each phase, and efficacy of intervention were analyzed.

[Use of antiretroviral drugs invoices for the follow-up of a treatment programme. Example in Abidjan, Côte d'Ivoire]. / Utilisation des factures des médicaments antirétroviraux pour le suivi d'un programme de traitement. Exemple a Abidjan, Côte-d'Ivoire.

A retrospective analysis of the prescriptions of the ARV treatment programme in Abidjan, Côte-d'Ivoire enabled the authors to assess the collected anonymous information in order to evaluate the efficacy of the programme. This collection of information helps to supervise each center at a lower cost, to alert on some working problems and to follow the quality of the observance. This supervision is possible regardless of the health care places, it can be carried out systematically from the administrative or financial services. In this study this follow-up reveals some problems.

[Antiretroviral drugs for the treatment and prevention of herpes infections in the year 2000]. / Place des antirétroviraux en 2000 dans le traitement et la prévention de l'infection herpétique.

Major developments in the two last decades have improved the diagnosis and the treatment of Herpes Simplex Virus infection. Aciclovir was the first effective antiherpetic drug available. Afterwards other drugs have been developed either with a better bioavailability or with an activity against aciclovir-resistant strains. Although there is at present no effective vaccine or drug capable of eradicating established infection, these antiviral drugs are able to shorten the course and decrease severity of symptomatic episodes in both normal and immunocompromised patients. Moreover in patients with frequently recurrent herpes a suppressive therapy will suppress episodes or decrease their frequency. The ongoing therapeutic research, beside the development of new drugs inhibiting viral replication, concerns the strengthening of specific immune response which should lead to the development of effective therapeutic and preventive vaccines.

Seroprevalence of HSV-1 and HSV-2 infection in the general French population.

BACKGROUND: In spite of the large prevalence and growing incidence of herpes simplex infection (HSV-1 and HSV-2), relatively few large serological surveys are available worldwide and it is still difficult compare frequencies of HSV contaminations in various countries. We present the results of HERPIMAX, the first epidemiological inquiry on HSV prevalence in the general French population. METHODS: Of a cohort of 12,735 presumed healthy adult volunteers included in the prospective study SU.VI.MAX, designed to assess the relation between nutritional supplementations and degenerative diseases, HERPIMAX randomly selected 4412 subjects (females 66.5%, males 33.5%). All serum samples were assessed for HSV-1 and HSV-2 IgG antibodies with a HSV type specific, enzyme immunosorbent assay (EIA). Equivocal result were retested with another HSV type specific immunoblot assay combined with a type common HSV IgG EIA in order to give a definitive interpretation. RESULTS: The mean seroprevalence was 67% for HSV-1 and 17.2% for HSV-2. For HSV-2 the seroprevalence was higher in females (17.9%) compared with males (13.7%) (p<0.001). For both HSV types, there was no significant difference in prevalence as regards age distribution in males and females, whereas prevalence increased significantly with age in females for HSV-1. Univariate analysis showed a significant association between HSV-1 prevalence and education level in males and females (p<0.001) and between HSV-2 prevalence and marital status in both sexes (p<0.001). There were geographical disparities, with a higher HSV-2 prevalence in the south of France as well as in Paris. CONCLUSION: These results confirm a high prevalence of HSV infection in France. They are also in agreement with previous results of other survey carried out in other developed countries as regards higher prevalence of HSV-2 infection in women, the stability of seroprevalence for both HSV types after 35 years of age in females and 45 years of age in males.

[Natural history of HSV1 and HSV2 transmission modes and epidemiology consequences of HSV infection on HIV infection. Prevention]. / Histoire naturelle de l'infection HSV1 et HSV2. Modes de transmission. Epidémiologie. Conséquences de l'herpès sur l'infection à HIV. Prévention.

Both Herpes simplex viruses HSV1 and HSV2 are transmitted by direct mucosal or cutaneo-mucosal contact between individuals. HSV1 is the leading cause of orofacial herpes and HSV2 the most frequently encountered cause of genital herpes. There are however a number of environmental and behavioral factors that modify the epidemiological pattern in both infections. These factors also affect virus dynamics and spread. In developing countries, HSV1 infections continues to be acquired in early childhood. In developed countries, displacement of this acquisition towards adolescence and adulthood explains, in part, the increase in genital herpes caused by HSV1. HVS2 infection progresses in the sexually active population worldwide. Although the rate of seroprevalance varies greatly from one continent to another, women are still more often infected than men. HSV2 genital infection is a cofactor for transmission and acquisition of HIV, which, in certain African regions where the two infections are highly prevalent, explains in part the progression of the HIV epidemic. Until a vaccine becomes available, the prevention depends on abstention from all oral and genital contact during periods of active disease. For genital herpes, use of a preservative has only a relative protective effect and the contribution of suppressive treatment in potentially contaminated subjects is under evaluation.

Famciclovir vs. aciclovir in immunocompetent patients with recurrent genital herpes infections: a parallel-groups, randomized, double-blind clinical trial.

BACKGROUND: Twice-daily therapy with famciclovir (FCV) was shown to be effective for episodic therapy for recurrent genital herpes in a large placebo-controlled trial. However, no study has been published to date comparing FCV and aciclovir (ACV). OBJECTIVES: We have evaluated the effectiveness of FCV vs. ACV in the treatment of recurrent genital herpes infection. METHODS: A multicentre, double-blind, double-placebo, randomized, parallel-design study, assessed for equivalence, was conducted. As the analysis was based on confidence intervals, a difference of lesion healing time between ACV and FCV (Delta) of 1.05 days with a standard deviation of 2.30 days was chosen. Two hundred and four outpatients were included. Patients self-initiated oral therapy with 125 mg of FCV twice daily or ACV 200 mg five times daily for 5 days. The principal end-point of the study was the complete healing of lesions. Duration of the complete resolution of all symptoms, and safety were also considered. RESULTS: The mean healing time was 5.1 days and 5.4 days for FCV and ACV, respectively, with a crude value of Delta = 0.25 days (CI 95%: -0.32; 0.82) in the intent-to-treat population. Therefore, the confidence interval for the difference between the two treatments lies entirely within the equivalence range (-1.05-1.05). The value of Delta in the per-protocol population [0.35 day (CI 95%: -0.24; 0.93)] was comparable between the two groups. No differences were detected in the proportion of patients having complete healing at the different days of evaluation as well as in the duration until the complete resolution of all the symptoms. The frequency, nature and severity of adverse events did not differ among the two treatment groups. CONCLUSIONS: Twice-daily FCV was as effective and safe in the treatment of recurrent genital herpes simplex virus infection as five times daily ACV.

In vitro inactivation of Chlamydia trachomatis and of a panel of DNA (HSV-2, CMV, adenovirus, BK virus) and RNA (RSV, enterovirus) viruses by the spermicide benzalkonium chloride.

Kinetics of inactivation by the detergent spermicide benzalkonium chloride (BZK) of Chlamydia trachomatis and of a panel of DNA viruses [herpes simplex virus hominis type 2 (HSV-2), cytomegalovirus (CMV), adenovirus (ADV) and BK virus (BKV)] and RNA [respiratory syncytial virus (RSV) and enterovirus (ENV)] were established in accordance with a standardized in vitro protocol. After a 5 min incubation, inactivation of >95% of HSV-2 and CMV was obtained at a concentration of 0.0025% (w/v) (25 Ig/L); concentrations as low as 0.0005%, 0.0050% and 0.0125%, induced a 3.0 log10 reduction in infectivity of HSV-2 and CMV, RSV and ADV, respectively. After a 60 min incubation, concentrations of 0.0125% and 0.050% provided a 3.0 log10 reduction in infectivity of ENV and BKV, respectively. These features indicate that sensitivity to BZK was very high (HSV-2 and CMV) or high (RSV) for enveloped viruses, intermediate (ADV) or low (ENV and BKV) for non-enveloped viruses. Furthermore, BZK had marked antichlamydial activity, showing >99% killing after only a 1 min incubation at a concentration of 0.00125%. BZK demonstrates potent in vitro activity against the majority of microorganisms causing sexually transmitted infectious diseases, including those acting as major genital cofactors of human immunodeficiency virus transmission. These attributes qualify BZK as a particularly attractive candidate for microbicide development.

Selection of drug-resistant variants in the female genital tract of human immunodeficiency virus type 1-infected women receiving antiretroviral therapy.

We investigated human immunodeficiency virus (HIV) type 1 RNA, proviral DNA, and antiretroviral drug-resistant variants in cervicovaginal secretions of HIV-1-infected women receiving antiretroviral therapy. The prevalence of detectable HIV-1 RNA in genital secretions was inversely related to the number of antiretroviral drugs taken by the patients. Proviral DNA was detected in approximately half of all samples of cervicovaginal secretions from HIV-1-infected women, regardless of the presence or absence of HIV-1 RNA in cervicovaginal secretions and of the antiretroviral regimen. In cervicovaginal secretions of most women with persisting genital viral replication, HIV variants exhibiting mutations associated with drug resistance against protease and reverse-transcriptase pol genes were found. Our observations indicate that antiretroviral therapy is not effective in purging the female genital tract of cell-associated provirus and that antiretroviral drugs that penetrate the female genital tract at suboptimal concentrations exert a potent selective pressure on genital HIV variants when local replication of free HIV-1 RNA persists.

[Agranulocytosis in acute hepatitis B in an HIV seropositive patient]. / Agranulocytose au cours d'une hépatite B aiguë chez un patient séropositif pour le VIH.

BACKGROUND: During the course of acute hepatitis B, hematology disorders are common though they are generally mild and occur early. Agranulocytosis is exceptional and occurs late in the disease course. CASE REPORT: We report a case of agranulocytosis which developed 3 weeks after onset of acute hepatitis B in an HIV-positive patient. Peripheral and central hematological disorders led to the diagnosis. Agranulocytosis developed during the cytolytic phase of the primary hepatitis B infection and regressed after administration of hematopoietic growth factors. DISCUSSION: It is sometimes difficult to establish the causal effect of hepatitis B in the development of agranulocytosis in patients with an HIV co-infection who are on a multiple drug regimen and subject to multiple bacterial, viral or parasite infections.

Quality of life and use of health care among people with genital herpes in France.

In order to assess psychological morbidity in France related to genital herpes infection, we carried out a transversal study comparing infected patients with a control group. A total of 236 patients with genital herpes were first identified by means of a postal survey, then matched against a witness group of 236 noninfected persons. Detailed questionnaires were sent out to each person in the 2 groups. A total of 150 herpes patients and 200 non-infected persons answered the questionnaire, which enabled us to measure the incidence of the disease by means of 2 indicators: a herpes-specific scale and the SF-36 quality of life questionnaire. Emotional trauma due to genital herpes was reported amongst 23% of the participants. Of the participants, 57% indicated that herpes interfered with their sexual relationships; 50% felt it difficult to live with genital herpes; and 37% felt that herpes ruins their lives. An analysis assessing health-related quality of life indicated significant differences between the scores of the 2 groups and showed that quality of life is lower amongst herpes patients. Respondents with genital herpes required more frequent consultations with GPs (81% vs. 73%), and significantly more frequent consultations with specialists (59% vs. 45%). Our study confirms that substantial psychological morbidity exists in patients with genital herpes.

Epidemiology of genital herpes - recent advances.

Genital herpes is a common, distressing infection which, due to increasing incidence world-wide, has become a prominent public health issue over recent years, even throughout the decade of human immunodeficiency virus (HIV). Since the late 1970's, the prevalence of herpes simplex virus type 2 (HSV-2) infection has increased by approximately 30 percent in the US. The number of sufferers world-wide is currently estimated at approximately 86 million people. New serological methods based on the detection of type-specific antibodies to herpes simplex virus (HSV) glycoproteins have clarified issues concerning the true incidence of genital herpes, the modifying effect of prior HSV-1 infections, the changing proportions of HSV-1 genital herpes, and the importance of asymptomatic shedding. Patients' ignorance of their diagnosis along with the occurrence of atypical symptomatology and asymptomatic viral shedding of HSV all contribute to the transmission of genital herpes. Genital ulcer disease, of which genital herpes is the most common cause in developed countries, is an important risk factor in the acquisition and transmission of human immunodeficiency virus (HIV) infection and has contributed to the spread of this disorder. Risk factors for genital herpes HSV-2 are strongly related to lifetime number of sexual partners, number of years of sexual activity, male homosexuality, black race, female gender and a history of previous sexually transmitted diseases (STD). Understanding the epidemiology of genital herpes is of great importance in limiting the spread of this STD. In this review, we summarise current knowledge related to the epidemiology of genital herpes.

'Brown sugar' heroin intoxication and improvement of surrogate immunologic markers in HIV infection.

OBJECTIVE: To report on the unexpected improvement in major biological surrogate markers (CD4 T-cell count, HIV RNA viral load, and apoptosis level) during the periods of 'brown sugar' heroin intoxication (BSI) in 12 HIV-1-infected intravenous drug users, independently of their antiretroviral therapy, compared to the period of 'brown sugar' heroin withdrawal (BSW). METHODS: The patients were followed prospectively for a total of 417 months over 4 years. Twenty-four episodes of BSI and 24 periods of BSW were analyzed. RESULTS: (1) BSI: the mean (+/-SE) duration was 9+/-1.8 months; at onset, the mean +/-SE CD4 T-cell count was 401+/-88/mm3; at the end, an absolute increase of 346 CD4 T-cells/mm3 and a CD4 T-cell count relative variation of +131% was observed. Half of the patients showed an increase of CD4 T-cell count of more than 90% during their follow-up. The mean+/-SE of CD8 T-cell count increased significantly by 108%. (2) BSW: the mean +/- SE duration was 8.4+/-1.3 months; at onset, the mean +/-SE CD4 T-cell count was 695+/-78/mm3; at the end, an absolute decrease of 342 CD4 T-cells/mm3 and a CD4 T-cell count relative variation of -52% was observed. Half of the patients showed a decrease of CD4 T-cell count of more than 51%. (3) Circulating viral load appeared to be significantly higher during BSW (median: 452 000 Eq RNA/mL) than during BSI (median: 52 000 Eq RNA/mL); p<0.01. (4) Similarly, the apoptotic process affecting circulating lymphocytes was significantly lower during BSI than during BSW episodes. (5) The 4-year mortality rate was 7%, compared with 36% in HIV-positive former drug users (p<0.001). CONCLUSIONS: Taken together, these features suggest that 'brown sugar' heroin could have either immunomodulatory or antiretroviral properties. Confirmation of these findings and investigation of the role of the many substances in 'brown sugar' heroin are indicated.

Evaluating the process of tailoring the global HIV/AIDS practice guidelines for use in developing countries.

OBJECTIVE: To describe a systematic procedure for adapting, or 'tailoring' the World Health Organisation's 'global guidelines for the management of HIV/AIDS in adults and children' for use in two developing countries: Malawi and Barbados. DESIGN: In order for these guidelines to achieve reproducibility, clinical flexibility, and clinical applicability, a systematic procedure is needed to tailor the guidelines to the local practice conditions of specific settings. METHODS: A group of local experts in each country used a nominal group process to modify the global program on AIDS (GPA) guidelines for local use. Semantic analysis techniques, known as clinical algorithm nosology (CAN), were used to compare the two modified guidelines with the global ones to determine the extent and type of differences between sets of guidelines. RESULTS: Standard, locally-tailored algorithm map guidelines (AMG) were developed within 4 months. CAN semantic analysis showed that guideline structure was maintained; 572/858 (66.6%) decision nodes were found to be the same in the GPA/Malawi, GPA/Barbados and Malawi/Barbados comparisons. However, different guideline versions managed patients quite differently, as evidenced by clinical algorithm patient abstraction (CAPA) scores of between 0 and 8.46 (0 = different; 8 = similar; 10 = identical). Analysis of the 197 specific differences found in these abstractions showed that 83% were in approaches to diagnosis and therapy, while the remaining 17% related to disease prevalence. CONCLUSIONS: Standard techniques involving consensus used to develop clinical guidelines can also be employed to tailor these guidelines to local settings. Semantic analysis shows that the tailoring preserves structure but may involve significant modification to the processes of clinical care that could in turn affect care outcomes.

Kinetics of Chlamydia trachomatis clearance in patients with azithromycin, as assessed by first void urine testing by PCR and transcription-mediated amplification.

METHODS: Test-of-cure of 19 patients with Chlamydia trachomatis genital infection was assessed by daily collection of first void urine for 7 days just after treatment by azithromycin single-dose. RESULTS: Detection by PCR and TMA of C. trachomatis showed a good correlation between both methods. The observation that post-therapy chlamydial nucleic acid detection is associated to bacterial clearance suggests that all the patients were cured.

Comparative prevalence, incidence and short-term prognosis of cervical squamous intraepithelial lesions amongst HIV-positive and HIV-negative women.

OBJECTIVE: To investigate the impact of HIV infection on the prevalence, incidence and short-term prognosis of squamous intraepithelial lesions (SIL), in a prospective study with 1-year follow-up. METHODS: Between 1993 and 1995, 271 HIV-positive and 171 HIV-negative women at high risk of HIV infection were recruited, 365 (82.6%) of whom completed the 1-year follow-up. The women underwent a Papanicolaou smear test at inclusion and at 6 and 12 months. Human papillomavirus (HPV) was detected at inclusion by Southern blot and PCR. RESULTS: The SIL prevalence ranged from 7.5% for HIV-negative to 31.3% for HIV-positive women with CD4 cell counts < 500 x 10(6)/l (P < 0.001). Other factors associated independently and significantly with SIL prevalence were HPV-16, 18, 33 and related types, HPV-31, -35, -39 and related types, lifetime number of partners, younger age, past history of SIL and lack of past cervical screening. The SIL incidence ranged from 4.9% in HIV-negative women to 27% in HIV-positive women with CD4 cells < 500 x 10(6)/l (P < 0.001). Progression from low- to high-grade SIL during follow-up was detected in 38.1% of HIV-positive women with CD4 cells < or = 500 x 10(6)/l but in no HIV-negative nor HIV-positive women with CD4 cells > 500 x 10(6)/l. HPV-16, 18, 33 and related types were also associated with higher incidence of SIL and progression from low- to high-grade SIL. CONCLUSION: HIV-induced immunodeficiency is associated with high prevalence, incidence and persistence/progression of SIL. A pejorative influence of HIV infection without marked immunodeficiency is less clear. HIV-positive women with SIL may thus benefit from early treatment when a useful immune response is still present.