Genital ulcers caused by herpes simplex virus | Enfermedades Infecciosas y Microbiología Clínica (English Edition)

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Adapted from Garland and Steben.<a class="elsevierStyleCrossRef" href="#bib0280">13</a>" ] ] ] "textoCompleto" => "Introduction: microbiology of HSVGenital herpes is a sexually transmitted disease caused by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), which belong to the herpesviridae family of DNA viruses.The herpes viruses have a well-defined structure, being composed of an icosahedral capsid surrounded by a tegument containing 15–20 proteins. The tegument is then in direct contact with the envelope, which is made up of numerous glycoproteins. The genome is a single linear double-stranded DNA molecule 152–155kbp in size. These two viruses share up to 40% homology in their genome structure, reaching up to 83% in the coding regions, which largely explains their antigenic cross-reactivity.<a class="elsevierStyleCrossRefs" href="#bib0220">1–3</a>The herpesviridae family is divided into three subfamilies: alpha, beta and gamma (based on biological and genomic similarities). The alphaherpesviruses include HSV-1, HSV-2 and varicella zoster virus (VZV). Humans are the only known reservoirs.HSV-1 is a large, neurotropic virus which causes mainly oral infections ranging from minor lesions, such as cold sores, to severe lesions, such as meningoencephalitis. HSV-2 is very similar, but it causes anogenital infections or neonatal herpes. In recent years, these data have varied as a consequence of oral sex practices, with HSV-2 manifesting in labial lesions and an increase in the prevalence of HSV-1 in anogenital infections. In the light of these changes, we need to break with the traditional assumptions that HSV-2 means genital herpes and that HSV-1 is limited to orolabial infections with non-sexual transmission.HSV lesions continue to be the most common cause of vulva ulcers in the sexually active population (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). A continuous increase in HSV infection has been detected in recent years, due in part to sociocultural changes and risky sexual practices. The majority of these infections are asymptomatic, which favours transmission.<a class="elsevierStyleCrossRef" href="#bib0235">4</a> Recent studies in sexually active people aged from 14 to 49 in the United States indicate that the prevalence of HSV-1 is 47.8%, while that of HSV-2 is 11.9%; both prevalences increase with age, and are higher in women than in men.<a class="elsevierStyleCrossRefs" href="#bib0240">5,6</a><elsevierMultimedia ident="fig0005"></elsevierMultimedia>WHO data estimate that, worldwide, 11% of the population aged from 15 to 49 is infected with HSV-2.<a class="elsevierStyleCrossRef" href="#bib0250">7</a> Meanwhile, we have to consider the potential for morbidity and mortality in the newborn due to the risk of transmission during pregnancy, and as a cofactor in the transmission of HIV.<a class="elsevierStyleCrossRef" href="#bib0255">8</a>PathogenesisThe infectious cycle of the virus starts after contact with the oral or genital mucosa, through abrasions or micro-cracks in the host's skin (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). Replication begins in the epidermis and penetrates sensory nerve endings in the skin. Through the axon of these nerves it is transported to the nucleus of the neurons in the sensory ganglia in the spinal cord (spinal or trigeminal). HSV can replicate within sensory ganglion neurons or remain dormant for months and even years, and reactivate spontaneously or in response to various stimuli (solar radiation, stress, fever, certain medications, acute diseases or immunosuppressive processes). This ability of the latent virus to reactivate is defined as recurrent HSV disease. When the virus is reactivated, it descends through the sensory nerve to the surface of the initially infected dermatomes (orolabial or vulva). Replication continues in the epidermal cells and can cause asymptomatic excretion in oral or genital secretions, or obvious clinical recurrence, resulting in vesicles and inflammation of local lymph nodes.<a class="elsevierStyleCrossRefs" href="#bib0260">9,10</a><elsevierMultimedia ident="fig0010"></elsevierMultimedia>Clinical manifestationsThe clinical signs and symptoms of genital herpes vary, depending on the type of HSV, gender, age, immune status of the patient and previous exposure to the virus. Episodes in patients with no evidence of previous HSV infection (primary infection) may be more severe on average than in patients with previous infection (non-primary first-episode genital herpes). However, more commonly, we find asymptomatic primary infections, meaning that most people with either genital or oral herpes are unaware of their infection status.<a class="elsevierStyleCrossRef" href="#bib0270">11</a>In the case of primary genital herpes we find that 7–50% of cases are caused by HSV-1 infection, while 50–93% are due to HSV-2. These proportions vary according to geographical location and socioeconomic status.<a class="elsevierStyleCrossRef" href="#bib0260">9</a> The incubation period is about 4 days (it can range from 2 to 12 days). In most cases, clinically visible lesions are preceded by a prodromal phase (2–24h before the lesions appear), which can manifest with fever, malaise, headache, myalgia, stinging or itchiness in the anal/genital area, abnormal vaginal discharge and pain in legs, buttocks or genitals. In immunocompetent women, lesions (blisters that can progress to ulcers) develop in areas of infection (vulva, cervix, vagina, perineum and/or urethra),<a class="elsevierStyleCrossRefs" href="#bib0275">12,13</a> causing urethritis and/or painful inguinal lymphadenopathy. The most common complications derive from extragenital skin lesions, central nervous system involvement and opportunistic fungal infections. Less frequently, sacral radiculomyelitis with urinary retention, transverse myelitis and neuralgia may occur. Complications are more common in women than in men.<a class="elsevierStyleCrossRefs" href="#bib0260">9,11</a>Both local and systemic symptoms are less severe and resolve more quickly in non-primary first-episode genital herpes than in primary infections.The average duration of viral shedding is 12 days in primary disease and 7 days in non-primary disease.Recurrent genital herpes is one of the main problems of this disease, as it depends on the type of virus, the intensity of the first episode and also the host. Most cases of recurrence occur in the first year after primary infection (80–90% for HSV-2 and 20% for HSV-1). There is a great deal of variation in the number of flare-ups, the severity and the natural course of recurrences.<a class="elsevierStyleCrossRefs" href="#bib0285">14,15</a>Skin manifestations tend to be in the same area of the first episode and are sometimes nonspecific and barely perceptible, such as fissures and cracks, which can lead to mistaken diagnosis. Occasionally, there may be no lesions, making it difficult to diagnose the recurrences. Systemic symptoms are rare and less severe, although they can be more painful and prolonged in women. The recurrence rate increases during pregnancy, but the course and duration are similar.<a class="elsevierStyleCrossRef" href="#bib0285">14</a>DiagnosisA clinical diagnosis is enough to start early empirical treatment and this improves the symptoms and shortens their duration. However, the diagnosis should always be confirmed with laboratory tests in order to deliver a prognosis and choose the optimal treatment.Physical examination involves external and internal examination of genitals, and checking for lymphadenopathy (hard, mobile, bilateral and very painful) and location of the virus in other areas (mouth and eyes), along with the patient's medical history. The initial lesion is one or more grouped vesicles on an erythematous base. These vesicles subsequently open up and lead to shallow ulcerations. In the area around the labia and rectum the vesicles often burst before they are noticed, and crusts may appear (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>). In primary genital infection, the pain tends to last 10 days and the lesions heal in 2–3 weeks. They are less painful and of limited duration.<elsevierMultimedia ident="fig0015"></elsevierMultimedia>The most commonly used diagnostic techniques are:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-Tzanck smear, from an unbroken vesicle. Cheap and quick tool, but requires experienced staff and is limited to this type of lesion.<a class="elsevierStyleCrossRefs" href="#bib0290">15,16</a></li><li class="elsevierStyleListItem" id="lsti0010">-Viral culture: although isolation in cell culture is relatively simple and fast compared to other viruses, the yield is higher in the presence of vesicles (80%) and when the samples are taken in the first two days after they appear, and lower in the crust phase or in recurrences (25–50%). It is a sensitive and specific, but lengthy, method. The characteristic cytopathic effects tend to appear within 12–48h.<a class="elsevierStyleCrossRefs" href="#bib0300">17,18</a></li><li class="elsevierStyleListItem" id="lsti0015">-Direct/indirect immunofluorescence techniques: fast, cheap techniques, many of them available fully automated or semi-automated, with a sensitivity-specificity of 85–99%.<a class="elsevierStyleCrossRefs" href="#bib0310">19–23</a></li><li class="elsevierStyleListItem" id="lsti0020">-Type-specific serology for specific anti-HSV IgG antibodies: relevant in patients with a history of undiagnosed atypical genital lesion, suspicion of partner infection with infected patient and pregnant women at risk of transmission to the newborn. These are also fast, inexpensive techniques, many of which are fully automated or semi-automated. However, the limitation is that the antibody for the viral glycoprotein is detected from 6 to 8 weeks and approximately 5% of the patients may have undetectable levels. They have high sensitivity (93–96%) and specificity (80–98%),<a class="elsevierStyleCrossRef" href="#bib0335">24</a> but their use is not recommended in asymptomatic patients, given the high rate of false positives in the low-risk population.</li><li class="elsevierStyleListItem" id="lsti0025">-A negative serology result may indicate both the absence of previous contact with HSV and absence of immune response, either due to initial phase of infection (primary infection) or alterations in the patient's immune system. In contrast, the presence of total antibodies is evidence of herpetic infection. A negative IgM indicates a non-active infection at the time of analysis, while the presence of IgM shows an evolving infection (not always a primary infection, as in some recurrences significant amounts of IgM may be detected).<a class="elsevierStyleCrossRefs" href="#bib0340">25,26</a></li><li class="elsevierStyleListItem" id="lsti0030">-PCR: use of PCR in clinical practice is booming thanks to the multiplex PCR technique that enables the simultaneous detection of the main organisms present in infectious ulcers of sexual origin (Treponema pallidum, Haemophilus ducreyi, Chlamydia trachomatis L serovar, which causes lymphogranuloma venereum, and HSV 1–2). This technique has a high sensitivity and specificity (both close to 100%), it is fast, its cost is decreasing and, combined with the fact that it is automated, it enables access for an increasing number of laboratories. Mainly because of its high sensitivity (even in cases with low viral load) it is useful for detecting viral shedding in asymptomatic patients and diagnosing lesions which were negative in the culture. The biggest drawback is the cost and the requirement for laboratories and specialised staff. Commercial kits are now available for the simultaneous determination of several STIs or exclusively herpes simplex infection which can differentiate between HSV types 1 and 2, something that a culture cannot do. For all these reasons, PCR has progressively displaced performing a culture as the diagnostic method for HSV infection.<a class="elsevierStyleCrossRefs" href="#bib0350">27,28</a></li></ul>The most commonly used molecular targets are conserved sequences of the genes encoding the surface glycoproteins gD and gB, or the enzymatic proteins DNA polymerase and thymidine kinase, with differences in their sequence which enable discrimination in the detection of HSV-1 and HSV-2, such as those approved by the FDA for the detection of HSV in genital lesions: IsoAmp HSV Assay (BioHelix Corporation), Multi-Code-RTx Herpes Simplex Virus 1 & 2 Kit (EraGen Biosciences Inc.) and BD ProbeTec Herpes Simplex Viruses HSV 1 & 2 (HSV QxAssays).<a class="elsevierStyleCrossRefs" href="#bib0360">29,30</a>TreatmentThe WHO recommends “empirical” or “syndromic” treatment, as the results of the diagnostic tests are not available at the time of the first consultation. Such early treatment can lead to faster healing, relief of symptoms and a reduced risk of transmission. It is recommended in patients with genital ulcers suggestive of HSV infection, but has the disadvantage of potentially being inappropriate treatment. It is therefore essential to follow up patients to assess their treatment response and diagnostic tests results and to reassess treatment decisions, if necessary.In the first episode of genital herpes, antivirals should be used for the first five days from onset of the episode, or during the formation of new lesions. The treatment of choice is oral antivirals, aciclovir, valaciclovir and famciclovir, which reduce the severity and duration of the episode (level of evidence Ib, A).<a class="elsevierStyleCrossRef" href="#bib0370">31</a> Topical treatments are not recommended, as they are less effective than oral treatments and can generate resistance (IV, C). The only indication for the use of intravenous therapy is when the patient cannot ingest or tolerate oral treatment. The recommended regimens for 5–10 days are as follows:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035">•Aciclovir 400mg three times a day, or aciclovir 200mg five times a day.</li><li class="elsevierStyleListItem" id="lsti0040">•Famciclovir 250mg three times a day.</li><li class="elsevierStyleListItem" id="lsti0045">•Valaciclovir 500mg twice a day.</li></ul>As treatment support measures, saline baths and the use of analgesics are recommended.In cases of recurrent genital herpes, the choice of treatment is made according to the severity of the symptoms and the time of recurrence.There is a range of treatment regimens, including the following:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0050">-Short therapy (Ib, A):<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0055">•Aciclovir 800mg three times a day for two days.</li><li class="elsevierStyleListItem" id="lsti0060">•Famciclovir 1g two tablets in a single day.</li><li class="elsevierStyleListItem" id="lsti0065">•Valaciclovir 500mg twice a day for three days.</li></ul></li><li class="elsevierStyleListItem" id="lsti0070">-Five-day treatment:<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0075">•Aciclovir 400mg three times a day for 3–5 days, or aciclovir 200mg five times a day.</li><li class="elsevierStyleListItem" id="lsti0080">•Valaciclovir 500mg twice a day.</li><li class="elsevierStyleListItem" id="lsti0085">•Famciclovir 125mg twice a day.</li></ul></li></ul>In special situations, such as HIV-positive patients, there are no clinical trials for the duration and treatment, so some clinicians opt for 10 days of treatment with twice the dose of any of the above oral treatments (IV, C). In pregnant women, treatment regimens and treatment management vary according to the trimester of virus acquisition.<a class="elsevierStyleCrossRefs" href="#bib0370">31,32</a>Suppressive therapy is recommended in patients with more than six episodes per year, and can reduce flare-ups by up to 70–80%.<a class="elsevierStyleCrossRef" href="#bib0370">31</a> This treatment regimen aims to reduce the number of recurrences and the risk of transmission to sexual partners. The recommended doses are:<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0090">-Aciclovir 400mg twice a day for five days.</li><li class="elsevierStyleListItem" id="lsti0095">-Valaciclovir 500mg a day (if fewer than 10 recurrences/year).</li><li class="elsevierStyleListItem" id="lsti0100">-Valaciclovir 1g a day (more than 10 recurrences/year).</li></ul>Recent studies indicate that topical microbicides, such as the 1% tenofovir or 3% SPL7013 gels, may be a promising option, having achieved a 51% reduction in the risk of HSV-2 infection.<a class="elsevierStyleCrossRefs" href="#bib0380">33,34</a> Another alternative is helicase-primase inhibitors, such as ASP2151, for the treatment of recurrent genital herpes.<a class="elsevierStyleCrossRefs" href="#bib0390">35,36</a>Therapeutic vaccines are another potential strategy for the management of HSV-positive patients, but few of the earlier trials obtained optimal results.<a class="elsevierStyleCrossRef" href="#bib0375">32</a> New trials focused on the immune response of the host, through the use of HSV peptides (HerpV), have achieved promising results in phase I and are now in phase I/IIa.<a class="elsevierStyleCrossRefs" href="#bib0400">37–40</a>Prophylactic vaccines have been under continuous development and improvement for years, prominent among which are two containing the HSV-2 glycoprotein D subunit, with a demonstrated efficacy of 73–74% among women seronegative for both types of HSV.<a class="elsevierStyleCrossRef" href="#bib0420">41</a>Analysis of health service costs related to HSV diseaseA recently published study<a class="elsevierStyleCrossRef" href="#bib0425">42</a> calculated the costs associated with HSV infection in hospital accident and emergency units. In the period 2006–2013 the cost amounted to 543 million dollars, going from 45 million dollars in 2006 to 91 million in 2013, primarily due to a 24% increase in the number of patients. The study emphasises the need for continuous prevention and patient sex education to avoid new cases.Level of evidenceFor more information and details about levels of evidence and grades of recommendation see: <a id="intr0010" class="elsevierStyleInterRef" href="http://www.iusti.org/regions/Europe/pdf/2013/Levels_of_Evidence.pdf">http://www.iusti.org/regions/Europe/pdf/2013/Levels_of_Evidence.pdf</a>Conflicts of interestThe author declares that there are no conflicts of interest regarding the research, authorship, and/or publication of this literature review." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1171314" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1095721" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1171313" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1095722" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction: microbiology of HSV" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Pathogenesis" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Clinical manifestations" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Diagnosis" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Treatment" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Analysis of health service costs related to HSV disease" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Level of evidence" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 12 => array:2 [ "identificador" => "xack400226" "titulo" => "Acknowledgements" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-09-22" "fechaAceptado" => "2018-10-11" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1095721" "palabras" => array:6 [ 0 => "Vaginitis" 1 => "Genital ulcers" 2 => "Herpes simplex virus" 3 => "Epidemiology" 4 => "Diagnosis" 5 => "Treatment" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1095722" "palabras" => array:6 [ 0 => "Vaginitis" 1 => "Úlceras genitales" 2 => "Virus herpes simplex" 3 => "Epidemiología" 4 => "Diagnóstico" 5 => "Tratamiento" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Genital herpes is a sexually transmitted disease caused by herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) belonging to the alphaherpesvirus family, that includes the varicella zoster virus. HSV infection continues to be the most common cause of vulvar ulcers among the sexually active population. Its incidence increases every year. This review summarises the microbiology of the virus, pathogenesis and infection in genitalia, clinical manifestations and correct identification, the different laboratory diagnostic methods, and choice of the correct treatment according to the first infection, recurrence or special cases. Finally, the cost of routine herpes simplex virus infection is analysed." ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "El herpes genital es una enfermedad de transmisión sexual causada por los virus herpes simplex tipo 1 (VHS-1) y tipo 2 (VHS-2), pertenecientes, junto al virus varicela zoster, a la familia alfaherpesviridae. La lesión por VHS continúa siendo la causa más frecuente de úlcera vulvar entre la población sexualmente activa, y su incidencia aumenta cada año. En esta revisión resumiremos la microbiología del virus, la patogenia y la infección en genitales, las manifestaciones clínicas para su correcta identificación, las diferentes técnicas diagnósticas de laboratorio y la elección del correcto tratamiento según sea primera infección, recurrencia o casos especiales. Finalmente, se discute un análisis de costes de la enfermedad por VHS." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Parra-Sánchez M. Úlceras genitales por virus herpes simplex. Enferm Infecc Microbiol Clin. 2019;37:260–264." ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1054 "Ancho" => 855 "Tamanyo" => 98130 ] ] "descripcion" => array:1 [ "en" => "Ulcerative vulvar lesions. Adapted from Garland and Steben.<a class="elsevierStyleCrossRef" href="#bib0280">13</a>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1369 "Ancho" => 2334 "Tamanyo" => 287990 ] ] "descripcion" => array:1 [ "en" => "Primary infection and reactivation. Adapted from Jaishankar and Shukla.<a class="elsevierStyleCrossRef" href="#bib0430">43</a>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 886 "Ancho" => 1504 "Tamanyo" => 92336 ] ] "descripcion" => array:1 [ "en" => "Course of symptoms and clinical manifestations in herpetic diseases. Adapted from Garland and Steben.<a class="elsevierStyleCrossRef" href="#bib0280">13</a>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:43 [ 0 => array:3 [ "identificador" => "bib0220" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Viral and cellular contributions to herpes simplex virus entry into the cell" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G. Campadelli-Fiume" 1 => "L. Menotti" 2 => "E. Avitabile" 3 => "T. Gianni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.coviro.2011.12.001" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Virol" "fecha" => "2012" "volumen" => "2" "paginaInicial" => "28" "paginaFinal" => "36" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22440963" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0225" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Epidemiology, clinical presentation, and antibody response to primary infection with herpes simplex virus type 1 and type 2 in young women" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.I. Bernstein" 1 => "A.R. Bellamy" 2 => "E.W. Hook" 3 => "M.J. Levin" 4 => "A. Wald" 5 => "M.G. Ewell" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/cid/cis891" "Revista" => array:6 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2013" "volumen" => "56" "paginaInicial" => "344" "paginaFinal" => "351" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23087395" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0230" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Topics in herpesvirus genomics and evolution" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D.J. McGeoch" 1 => "F.J. Rixon" 2 => "A.J. Davison" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.virusres.2006.01.002" "Revista" => array:6 [ "tituloSerie" => "Virus Res" "fecha" => "2006" "volumen" => "117" "paginaInicial" => "90" "paginaFinal" => "104" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16490275" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0235" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increasing role of herpes simplex virus type 1 in first episode anogenital herpes in heterosexual women and younger men who have sex with men, 1992–2006" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "N. Ryder" 1 => "F. Jin" 2 => "A.M. McNulty" 3 => "A.E. Grulich" 4 => "B. Donovan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/sti.2008.033902" "Revista" => array:6 [ "tituloSerie" => "Sex Transm Infect" "fecha" => "2009" "volumen" => "85" "paginaInicial" => "416" "paginaFinal" => "419" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19273479" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0240" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prevalence of herpes simplex virus type 1 and type 2 in persons aged 14–49: United States, 2015–2016" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G. McQuillan" 1 => "D. Kruszon-Moran" 2 => "E.W. Flagg" 3 => "R. Paulose-Ram" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "NCHS Data Brief" "fecha" => "2018" "volumen" => "304" "paginaInicial" => "1" "paginaFinal" => "8" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0245" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 2012" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.J. Looker" 1 => "A.S. Magaret" 2 => "M.T. May" 3 => "K.M.E. Turner" 4 => "P. Vickerman" 5 => "S.L. Gottlieb" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "PLOS ONE" "fecha" => "2015" "volumen" => "10" "paginaInicial" => "1" "paginaFinal" => "17" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0250" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Available from: <a class="elsevierStyleInterRef" target="_blank" id="intr0015" href="https://www.ncbi.nlm.nih.gov/books/NBK396232/">https://www.ncbi.nlm.nih.gov/books/NBK396232/</a> [accessed 01.09.18]" "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "WHO guidelines for the treatment of genital herpes simplex virus" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2016" "editorial" => "World Health Organization" "editorialLocalizacion" => "Geneva" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0255" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Herpes simplex virus: the interplay between HSV, host, and HIV-1" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.V. Desai" 1 => "S.S. Kulkarni" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1089/vim.2015.0012" "Revista" => array:6 [ "tituloSerie" => "Viral Immunol" "fecha" => "2015" "volumen" => "28" "paginaInicial" => "546" "paginaFinal" => "555" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26331265" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0260" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genital herpes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R. Gupta" 1 => "T. Warren" 2 => "A. Wald" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(07)61908-4" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2007" "volumen" => "370" "paginaInicial" => "2127" "paginaFinal" => "2137" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18156035" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0265" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "AEPCC-Guía: Infecciones del tracto genital inferior" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Alsina" 1 => "O. Arencibia" 2 => "C. Centeno" 3 => "P. de la Cueva" 4 => "I. Fuertes" 5 => "P. Fusté" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:4 [ "fecha" => "2016" "paginaInicial" => "1" "paginaFinal" => "66" "editorial" => "Publicaciones AEPCC" ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0270" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "An inquiry into the molecular basis of HSV latency and reactivation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "B. Roizman" 1 => "R.J. Whitley" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1146/annurev-micro-092412-155654" "Revista" => array:6 [ "tituloSerie" => "Annu Rev Microbiol" "fecha" => "2013" "volumen" => "67" "paginaInicial" => "355" "paginaFinal" => "374" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24024635" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0275" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "F. Xu" 1 => "M.R. Sternberg" 2 => "B.J. Kottiri" 3 => "G.M. McQuillan" 4 => "F.K. Lee" 5 => "A.J. Nahmias" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.296.8.964" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2006" "volumen" => "296" "paginaInicial" => "964" "paginaFinal" => "973" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16926356" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0280" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genital herpes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S.M. Garland" 1 => "M. Steben" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bpobgyn.2014.07.015" "Revista" => array:6 [ "tituloSerie" => "Best Pract Res Clin Obstet Gynaecol" "fecha" => "2014" "volumen" => "28" "paginaInicial" => "1098" "paginaFinal" => "1110" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25153069" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0285" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Optimal management of genital herpes: current perspectives" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "A. Sauerbrei" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2147/IDR.S96164" "Revista" => array:6 [ "tituloSerie" => "Infect Drug Resist" "fecha" => "2016" "volumen" => "9" "paginaInicial" => "129" "paginaFinal" => "141" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27358569" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0290" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical practice. Genital herpes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D. Kimberlim" 1 => "D. Rouse" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMcp023065" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2004" "volumen" => "350" "paginaInicial" => "1970" "paginaFinal" => "1977" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15128897" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0295" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The value of Tzanck smear test in diagnosis of erosive, vesicular, bullous, and pustular skin lesions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "M. Durdu" 1 => "M. Baba" 2 => "D. Seçkin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jaad.2008.07.059" "Revista" => array:6 [ "tituloSerie" => "J Am Acad Dermatol" "fecha" => "2008" "volumen" => "59" "paginaInicial" => "958" "paginaFinal" => "964" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18929431" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0300" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Herpes simplex virus detection from genital lesions: a comparative study using antigen detection (HerpChek) and culture" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R.W. Cone" 1 => "P.D. Swenson" 2 => "A.C. Hobson" 3 => "M. Remington" 4 => "L. Corey" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Clin Microbiol" "fecha" => "1993" "volumen" => "31" "paginaInicial" => "1774" "paginaFinal" => "1776" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8394375" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0305" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparative clinical evaluation of the IsoAmp® HSV Assay with ELVIS® HSV culture/ID/typing test system for the detection of herpes simplex virus in genital and oral lesions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "N.S. Miller" 1 => "B. Yen-Lieberman" 2 => "M.D. Poulter" 3 => "Y.W. Tang" 4 => "P.A. Granato" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcv.2012.04.004" "Revista" => array:6 [ "tituloSerie" => "J Clin Virol" "fecha" => "2012" "volumen" => "54" "paginaInicial" => "355" "paginaFinal" => "358" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22613012" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0310" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Detection of type-specific antibodies to HSV-1 and HSV-2: comparative analysis of a chemiluminescence immunoassay with a conventional ELISA" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "A.W. Maters" 1 => "C.V. Wright" 2 => "M.T. Lee" 3 => "G. Schwichtenberg" 4 => "B. Detrick" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.diagmicrobio.2012.03.023" "Revista" => array:6 [ "tituloSerie" => "Diagn Microbiol Infect Dis" "fecha" => "2012" "volumen" => "73" "paginaInicial" => "273" "paginaFinal" => "274" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22534561" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0315" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Comparison of commercial methods of immunoblot ELISA, and chemiluminescent immunoassay for detecting type-specific herpes simplex viruses-1 and -2 IgG" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "F. De Ory" 1 => "M.E. Guisasola" 2 => "P. Balfagón" 3 => "J.C. Sanz" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Clin Lab Anal" "fecha" => "2018" "volumen" => "32" "paginaInicial" => "e22203" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0320" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Development of a time-resolved fluorescence immunoassay for herpes simplex virus type 1 and type 2 IgG antibodies" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Q.N. Liang" 1 => "J.W. Zhou" 2 => "T.C. Liu" 3 => "G.F. Lin" 4 => "Z.N. Dong" 5 => "Z.H. Chen" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/bio.2800" "Revista" => array:6 [ "tituloSerie" => "Luminescence" "fecha" => "2015" "volumen" => "30" "paginaInicial" => "649" "paginaFinal" => "654" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25377426" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0325" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Evaluation of commercial herpes simplex virus IgG and IgM enzyme immunoassays" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "K. Liermann" 1 => "A. Schäfler" 2 => "A. Henke" 3 => "A. Sauerbrei" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jviromet.2014.01.001" "Revista" => array:6 [ "tituloSerie" => "J Virol Methods" "fecha" => "2014" "volumen" => "199" "paginaInicial" => "29" "paginaFinal" => "34" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24418499" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0330" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Performance of commercial enzyme-linked immunoassays for diagnosis of herpes simplex virus-1 and herpes simplex virus-2 infection in a clinical setting" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E. Agyemang" 1 => "Q.A. Le" 2 => "T. Warren" 3 => "A.S. Magaret" 4 => "S. Selke" 5 => "C. Johnston" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/OLQ.0000000000000689" "Revista" => array:6 [ "tituloSerie" => "Sex Transm Dis" "fecha" => "2017" "volumen" => "44" "paginaInicial" => "763" "paginaFinal" => "767" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28876290" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0335" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serological testing for herpes simplex virus (HSV)-1 and HSV-2 infection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Wald" 1 => "R. Ashley-Morrow" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1086/342104" "Revista" => array:7 [ "tituloSerie" => "Clin Infect Dis" "fecha" => "2002" "volumen" => "35" "numero" => "Suppl. 2" "paginaInicial" => "S173" "paginaFinal" => "S182" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12353203" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib0340" "etiqueta" => "25" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serological profile of HSV-2 in STD patients: evaluation of diagnostic utility of HSV-2 IgM and IgG detection" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "V.P. Amudha" 1 => "Rashetha" 2 => "G. Sucilathangam" 3 => "B. Cinthujah" 4 => "C. Revathy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7860/JCDR/2014/10586.5314" "Revista" => array:6 [ "tituloSerie" => "J Clin Diagn Res" "fecha" => "2014" "volumen" => "8" "paginaInicial" => "DC16" "paginaFinal" => "DC19" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25653947" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib0345" "etiqueta" => "26" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Serologic screening for genital herpes: an updated evidence report and systematic review for the US Preventive Services Task Force" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Feltner" 1 => "C. Grodensky" 2 => "C. Ebel" 3 => "J.C. Middleton" 4 => "R.P. Harris" 5 => "M. Ashok" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/jama.2016.17138" "Revista" => array:6 [ "tituloSerie" => "JAMA" "fecha" => "2016" "volumen" => "316" "paginaInicial" => "2531" "paginaFinal" => "2543" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27997660" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib0350" "etiqueta" => "27" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnostics for herpes simplex virus: is PCR the new gold standard?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L.B. Strick" 1 => "A. Wald" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/BF03256439" "Revista" => array:6 [ "tituloSerie" => "Mol Diagn Ther" "fecha" => "2006" "volumen" => "10" "paginaInicial" => "17" "paginaFinal" => "28" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16646574" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib0355" "etiqueta" => "28" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Diagnosis of genital herpes by real time PCR in routine clinical practice" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Ramaswamy" 1 => "C. McDonald" 2 => "M. Smith" 3 => "D. Thomas" 4 => "S. Maxwell" 5 => "M. Tenant-Flowers" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/sti.2003.008201" "Revista" => array:6 [ "tituloSerie" => "Sex Transm Infect" "fecha" => "2004" "volumen" => "80" "paginaInicial" => "406" "paginaFinal" => "410" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15459412" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib0360" "etiqueta" => "29" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Automated processing, extraction and detection of herpes simplex virus types 1 and 2: a comparative evaluation of three commercial platforms using clinical specimens" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.J. Binnicker" 1 => "M.J. Espy" 2 => "B. Duresko" 3 => "C. Irish" 4 => "J. Mandrekar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcv.2017.02.006" "Revista" => array:6 [ "tituloSerie" => "J Clin Virol" "fecha" => "2017" "volumen" => "89" "paginaInicial" => "30" "paginaFinal" => "33" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28226272" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib0365" "etiqueta" => "30" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A European multi-centre External Quality Assessment (EQA) study on phenotypic and genotypic methods used for Herpes Simplex Virus (HSV) drug resistance testing" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "B. Afshar" 1 => "D.F. Bibby" 2 => "R. Piorkowska" 3 => "N. Ohemeng-Kumi" 4 => "R. Snoeck" 5 => "G. Andrei" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.jcv.2017.10.002" "Revista" => array:6 [ "tituloSerie" => "J Clin Virol" "fecha" => "2017" "volumen" => "96" "paginaInicial" => "89" "paginaFinal" => "93" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29031157" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib0370" "etiqueta" => "31" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "2017 European guidelines for the management of genital herpes" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Patel" 1 => "O.J. Kennedy" 2 => "E. Clarke" 3 => "A. Geretti" 4 => "A. Nilsen" 5 => "S. Lautenschlager" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1177/0956462417727194" "Revista" => array:6 [ "tituloSerie" => "Int J STD AIDS" "fecha" => "2017" "volumen" => "28" "paginaInicial" => "1366" "paginaFinal" => "1379" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28836892" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib0375" "etiqueta" => "32" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Current thinking on genital herpes" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "A.M. Hofstetter" 1 => "S.L. Rosenthal" 2 => "L.R. Stanberry" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/QCO.0000000000000029" "Revista" => array:6 [ "tituloSerie" => "Curr Opin Infect Dis" "fecha" => "2014" "volumen" => "27" "paginaInicial" => "75" "paginaFinal" => "83" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24335720" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib0380" "etiqueta" => "33" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Q. Abdool Karim" 1 => "S.S. Abdool Karim" 2 => "J.A. Frohlich" 3 => "A.C. Grobler" 4 => "C. Baxter" 5 => "L.E. Mansoor" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/science.1193748" "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "2010" "volumen" => "329" "paginaInicial" => "1168" "paginaFinal" => "1174" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20643915" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib0385" "etiqueta" => "34" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A phase I randomized placebo controlled trial of the safety of 3% SPL7013 Gel (VivaGel®) in healthy young women administered twice daily for 14 days" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.R. Cohen" 1 => "J. Brown" 2 => "A.B. Moscicki" 3 => "E.A. Bukusi" 4 => "J.R. Paull" 5 => "C.F. Price" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1371/journal.pone.0016258" "Revista" => array:5 [ "tituloSerie" => "PLoS ONE" "fecha" => "2011" "volumen" => "6" "paginaInicial" => "e16258" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21311578" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib0390" "etiqueta" => "35" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Recent developments in antiherpesvirus drugs" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "H.J. Field" 1 => "R.A. Vere Hodge" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/bmb/ldt011" "Revista" => array:6 [ "tituloSerie" => "Br Med Bull" "fecha" => "2013" "volumen" => "106" "paginaInicial" => "213" "paginaFinal" => "249" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23596085" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib0395" "etiqueta" => "36" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "ASP2151 for the treatment of genital herpes: a randomized, double-blind, placebo- and valacyclovir-controlled, dose-finding study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Tyring" 1 => "A. Wald" 2 => "N. Zadeikis" 3 => "S. Dhadda" 4 => "K. Takenouchi" 5 => "R. Rorig" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1093/infdis/jis019" "Revista" => array:6 [ "tituloSerie" => "J Infect Dis" "fecha" => "2012" "volumen" => "205" "paginaInicial" => "1100" "paginaFinal" => "1110" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22351940" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib0400" "etiqueta" => "37" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A heat shock protein based polyvalent vaccine targeting HSV-2: CD4(+) and CD8(+) cellular immunity and protective efficacy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Mo" 1 => "C. Musselli" 2 => "H. Chen" 3 => "J. Pappas" 4 => "K. Leclair" 5 => "A. Liu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.vaccine.2011.07.011" "Revista" => array:6 [ "tituloSerie" => "Vaccine" "fecha" => "2011" "volumen" => "29" "paginaInicial" => "8530" "paginaFinal" => "8541" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21767588" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib0405" "etiqueta" => "38" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Wald" 1 => "D.M. Koelle" 2 => "K. Fife" 3 => "T. Warren" 4 => "K. Leclair" 5 => "R.M. Chicz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.vaccine.2011.09.046" "Revista" => array:6 [ "tituloSerie" => "Vaccine" "fecha" => "2011" "volumen" => "29" "paginaInicial" => "8520" "paginaFinal" => "8529" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21945262" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib0410" "etiqueta" => "39" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Biological efficacy study of HerpV vaccine with QS-21 to treat subjects with recurrent genital herpes. Available from: <a id="intr0020" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/ct2/show/NCT01687595?term=Biological+efficacy+study+of+HerpV+vaccine+with+QS21+to+treat+subjects+with+recurrent+genital+herpes%26rank=1">https://clinicaltrials.gov/ct2/show/NCT01687595?term=Biological+efficacy+study+of+HerpV+vaccine+with+QS21+to+treat+subjects+with+recurrent+genital+herpes&rank=1</a> [accessed 08.09.18]." ] ] ] 39 => array:3 [ "identificador" => "bib0415" "etiqueta" => "40" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Safety and immunogenicity study of therapeutic HSV-2 vaccine. Available from: <a id="intr0025" class="elsevierStyleInterRef" href="https://clinicaltrials.gov/ct2/show/NCT01667341">https://clinicaltrials.gov/ct2/show/NCT01667341</a> [accessed 08.09.18]." ] ] ] 40 => array:3 [ "identificador" => "bib0420" "etiqueta" => "41" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy results of a trial of a herpes simplex vaccine" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.B. Belshe" 1 => "P.A. Leone" 2 => "D.I. Bernstein" 3 => "A. Wald" 4 => "M.J. Levin" 5 => "J.T. Stapleton" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1103151" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2012" "volumen" => "366" "paginaInicial" => "34" "paginaFinal" => "43" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22216840" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib0425" "etiqueta" => "42" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cost of routine herpes simplex virus infection visits to U.S Emergency Departments 2006–2013" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "F. Di Xia" 1 => "M. Fuhlbrigge" 2 => "E. Dommasch" 3 => "C. Joyce" 4 => "A. Mostaghimi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.5811/westjem.2018.3.37543" "Revista" => array:6 [ "tituloSerie" => "West J Emerg Med" "fecha" => "2018" "volumen" => "19" "paginaInicial" => "689" "paginaFinal" => "692" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30013705" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib0430" "etiqueta" => "43" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genital herpes: insights into sexually transmitted infectious disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D. Jaishankar" 1 => "D. Shukla" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.15698/mic2016.09.528" "Revista" => array:6 [ "tituloSerie" => "Microb Cell" "fecha" => "2016" "volumen" => "3" "paginaInicial" => "438" "paginaFinal" => "450" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28357380" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack400226" "titulo" => "Acknowledgements" "texto" => "The author would like to thank Ms Morilla for revising and commenting on this literature review." 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CONTINUING MEDICAL EDUCATION: SEXUALLY TRANSMITTED INFECTIONS

Genital ulcers caused by herpes simplex virus

Úlceras genitales por virus herpes simplex

Manuel Parra-Sánchez

Molecular Diagnostics Deparment, Vircell Microbiologists, Parque Tecnológico de la Salud, Granada, Spain

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In the light of these changes&#44; we need to break with the traditional assumptions that HSV-2 means genital herpes and that HSV-1 is limited to orolabial infections with non-sexual transmission&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">HSV lesions continue to be the most common cause of vulva ulcers in the sexually active population &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; A continuous increase in HSV infection has been detected in recent years&#44; due in part to sociocultural changes and risky sexual practices&#46; The majority of these infections are asymptomatic&#44; which favours transmission&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">4</span></a> Recent studies in sexually active people aged from 14 to 49 in the United States indicate that the prevalence of HSV-1 is 47&#46;8&#37;&#44; while that of HSV-2 is 11&#46;9&#37;&#59; both prevalences increase with age&#44; and are higher in women than in men&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">5&#44;6</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0030" class="elsevierStylePara elsevierViewall">WHO data estimate that&#44; 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Complications are more common in women than in men&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">9&#44;11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Both local and systemic symptoms are less severe and resolve more quickly in non-primary first-episode genital herpes than in primary infections&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The average duration of viral shedding is 12 days in primary disease and 7 days in non-primary disease&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Recurrent genital herpes is one of the main problems of this disease&#44; as it depends on the type of virus&#44; the intensity of the first episode and also the host&#46; Most cases of recurrence occur in the first year after primary infection &#40;80&#8211;90&#37; for HSV-2 and 20&#37; for HSV-1&#41;&#46; There is a great deal of variation in the number of flare-ups&#44; the severity and the natural course of recurrences&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">14&#44;15</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Skin manifestations tend to be in the same area of the first episode and are sometimes nonspecific and barely perceptible&#44; such as fissures and cracks&#44; which can lead to mistaken diagnosis&#46; Occasionally&#44; there may be no lesions&#44; making it difficult to diagnose the recurrences&#46; Systemic symptoms are rare and less severe&#44; although they can be more painful and prolonged in women&#46; The recurrence rate increases during pregnancy&#44; but the course and duration are similar&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">14</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Diagnosis</span><p id="par0070" class="elsevierStylePara elsevierViewall">A clinical diagnosis is enough to start early empirical treatment and this improves the symptoms and shortens their duration&#46; However&#44; the diagnosis should always be confirmed with laboratory tests in order to deliver a prognosis and choose the optimal treatment&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Physical examination involves external and internal examination of genitals&#44; and checking for lymphadenopathy &#40;hard&#44; mobile&#44; bilateral and very painful&#41; and location of the virus in other areas &#40;mouth and eyes&#41;&#44; along with the patient&#39;s medical history&#46; The initial lesion is one or more grouped vesicles on an erythematous base&#46; These vesicles subsequently open up and lead to shallow ulcerations&#46; In the area around the labia and rectum the vesicles often burst before they are noticed&#44; and crusts may appear &#40;<a class="elsevierStyleCrossRef" href="#fig0015">Fig&#46; 3</a>&#41;&#46; In primary genital infection&#44; the pain tends to last 10 days and the lesions heal in 2&#8211;3 weeks&#46; They are less painful and of limited duration&#46;</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">The most commonly used diagnostic techniques are&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall">Tzanck smear&#44; from an unbroken vesicle&#46; Cheap and quick tool&#44; but requires experienced staff and is limited to this type of lesion&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">15&#44;16</span></a></p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0090" class="elsevierStylePara elsevierViewall">Viral culture&#58; although isolation in cell culture is relatively simple and fast compared to other viruses&#44; the yield is higher in the presence of vesicles &#40;80&#37;&#41; and when the samples are taken in the first two days after they appear&#44; and lower in the crust phase or in recurrences &#40;25&#8211;50&#37;&#41;&#46; It is a sensitive and specific&#44; but lengthy&#44; method&#46; The characteristic cytopathic effects tend to appear within 12&#8211;48<span class="elsevierStyleHsp" style=""></span>h&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">17&#44;18</span></a></p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0095" class="elsevierStylePara elsevierViewall">Direct&#47;indirect immunofluorescence techniques&#58; fast&#44; cheap techniques&#44; many of them available fully automated or semi-automated&#44; with a sensitivity-specificity of 85&#8211;99&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">19&#8211;23</span></a></p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall">Type-specific serology for specific anti-HSV IgG antibodies&#58; relevant in patients with a history of undiagnosed atypical genital lesion&#44; suspicion of partner infection with infected patient and pregnant women at risk of transmission to the newborn&#46; These are also fast&#44; inexpensive techniques&#44; many of which are fully automated or semi-automated&#46; However&#44; the limitation is that the antibody for the viral glycoprotein is detected from 6 to 8 weeks and approximately 5&#37; of the patients may have undetectable levels&#46; They have high sensitivity &#40;93&#8211;96&#37;&#41; and specificity &#40;80&#8211;98&#37;&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">24</span></a> but their use is not recommended in asymptomatic patients&#44; given the high rate of false positives in the low-risk population&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0105" class="elsevierStylePara elsevierViewall">A negative serology result may indicate both the absence of previous contact with HSV and absence of immune response&#44; either due to initial phase of infection &#40;primary infection&#41; or alterations in the patient&#39;s immune system&#46; In contrast&#44; the presence of total antibodies is evidence of herpetic infection&#46; A negative IgM indicates a non-active infection at the time of analysis&#44; while the presence of IgM shows an evolving infection &#40;not always a primary infection&#44; as in some recurrences significant amounts of IgM may be detected&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0340"><span class="elsevierStyleSup">25&#44;26</span></a></p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0110" class="elsevierStylePara elsevierViewall">PCR&#58; use of PCR in clinical practice is booming thanks to the multiplex PCR technique that enables the simultaneous detection of the main organisms present in infectious ulcers of sexual origin &#40;<span class="elsevierStyleItalic">Treponema pallidum</span>&#44; <span class="elsevierStyleItalic">Haemophilus ducreyi</span>&#44; <span class="elsevierStyleItalic">Chlamydia trachomatis L serovar</span>&#44; which causes lymphogranuloma venereum&#44; and HSV 1&#8211;2&#41;&#46; This technique has a high sensitivity and specificity &#40;both close to 100&#37;&#41;&#44; it is fast&#44; its cost is decreasing and&#44; combined with the fact that it is automated&#44; it enables access for an increasing number of laboratories&#46; Mainly because of its high sensitivity &#40;even in cases with low viral load&#41; it is useful for detecting viral shedding in asymptomatic patients and diagnosing lesions which were negative in the culture&#46; The biggest drawback is the cost and the requirement for laboratories and specialised staff&#46; Commercial kits are now available for the simultaneous determination of several STIs or exclusively herpes simplex infection which can differentiate between HSV types 1 and 2&#44; something that a culture cannot do&#46; For all these reasons&#44; PCR has progressively displaced performing a culture as the diagnostic method for HSV infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0350"><span class="elsevierStyleSup">27&#44;28</span></a></p></li></ul></p><p id="par0115" class="elsevierStylePara elsevierViewall">The most commonly used molecular targets are conserved sequences of the genes encoding the surface glycoproteins gD and gB&#44; or the enzymatic proteins DNA polymerase and thymidine kinase&#44; with differences in their sequence which enable discrimination in the detection of HSV-1 and HSV-2&#44; such as those approved by the FDA for the detection of HSV in genital lesions&#58; IsoAmp HSV Assay &#40;BioHelix Corporation&#41;&#44; Multi-Code-RTx Herpes Simplex Virus 1 &#38; 2 Kit &#40;EraGen Biosciences Inc&#46;&#41; and BD ProbeTec Herpes Simplex Viruses HSV 1 &#38; 2 &#40;HSV QxAssays&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">29&#44;30</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Treatment</span><p id="par0120" class="elsevierStylePara elsevierViewall">The WHO recommends &#8220;empirical&#8221; or &#8220;syndromic&#8221; treatment&#44; as the results of the diagnostic tests are not available at the time of the first consultation&#46; Such early treatment can lead to faster healing&#44; relief of symptoms and a reduced risk of transmission&#46; It is recommended in patients with genital ulcers suggestive of HSV infection&#44; but has the disadvantage of potentially being inappropriate treatment&#46; It is therefore essential to follow up patients to assess their treatment response and diagnostic tests results and to reassess treatment decisions&#44; if necessary&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">In the <span class="elsevierStyleItalic">first episode of genital herpes</span>&#44; antivirals should be used for the first five days from onset of the episode&#44; or during the formation of new lesions&#46; The treatment of choice is oral antivirals&#44; aciclovir&#44; valaciclovir and famciclovir&#44; which reduce the severity and duration of the episode &#40;level of evidence Ib&#44; A&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">31</span></a> Topical treatments are not recommended&#44; as they are less effective than oral treatments and can generate resistance &#40;IV&#44; C&#41;&#46; The only indication for the use of intravenous therapy is when the patient cannot ingest or tolerate oral treatment&#46; The recommended regimens for 5&#8211;10 days are as follows&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">&#8226;</span><p id="par0130" class="elsevierStylePara elsevierViewall">Aciclovir 400<span class="elsevierStyleHsp" style=""></span>mg three times a day&#44; or aciclovir 200<span class="elsevierStyleHsp" style=""></span>mg five times a day&#46;</p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#8226;</span><p id="par0135" class="elsevierStylePara elsevierViewall">Famciclovir 250<span class="elsevierStyleHsp" style=""></span>mg three times a day&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">&#8226;</span><p id="par0140" class="elsevierStylePara elsevierViewall">Valaciclovir 500<span class="elsevierStyleHsp" style=""></span>mg twice a day&#46;</p></li></ul></p><p id="par0145" class="elsevierStylePara elsevierViewall">As treatment support measures&#44; saline baths and the use of analgesics are recommended&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">In cases of <span class="elsevierStyleItalic">recurrent genital herpes</span>&#44; the choice of treatment is made according to the severity of the symptoms and the time of recurrence&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">There is a range of treatment regimens&#44; including the following&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0160" class="elsevierStylePara elsevierViewall">Short therapy &#40;Ib&#44; A&#41;&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">&#8226;</span><p id="par0165" class="elsevierStylePara elsevierViewall">Aciclovir 800<span class="elsevierStyleHsp" style=""></span>mg three times a day for two days&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">&#8226;</span><p id="par0170" class="elsevierStylePara elsevierViewall">Famciclovir 1<span class="elsevierStyleHsp" style=""></span>g two tablets in a single day&#46;</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">&#8226;</span><p id="par0175" class="elsevierStylePara elsevierViewall">Valaciclovir 500<span class="elsevierStyleHsp" style=""></span>mg twice a day for three days&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0180" class="elsevierStylePara elsevierViewall">Five-day treatment&#58;<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">&#8226;</span><p id="par0185" class="elsevierStylePara elsevierViewall">Aciclovir 400<span class="elsevierStyleHsp" style=""></span>mg three times a day for 3&#8211;5 days&#44; or aciclovir 200<span class="elsevierStyleHsp" style=""></span>mg five times a day&#46;</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">&#8226;</span><p id="par0190" class="elsevierStylePara elsevierViewall">Valaciclovir 500<span class="elsevierStyleHsp" style=""></span>mg twice a day&#46;</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">&#8226;</span><p id="par0195" class="elsevierStylePara elsevierViewall">Famciclovir 125<span class="elsevierStyleHsp" style=""></span>mg twice a day&#46;</p></li></ul></p></li></ul></p><p id="par0200" class="elsevierStylePara elsevierViewall">In special situations&#44; such as HIV-positive patients&#44; there are no clinical trials for the duration and treatment&#44; so some clinicians opt for 10 days of treatment with twice the dose of any of the above oral treatments &#40;IV&#44; C&#41;&#46; In pregnant women&#44; treatment regimens and treatment management vary according to the trimester of virus acquisition&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">31&#44;32</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Suppressive therapy</span> is recommended in patients with more than six episodes per year&#44; and can reduce flare-ups by up to 70&#8211;80&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">31</span></a> This treatment regimen aims to reduce the number of recurrences and the risk of transmission to sexual partners&#46; The recommended doses are&#58;<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">-</span><p id="par0210" class="elsevierStylePara elsevierViewall">Aciclovir 400<span class="elsevierStyleHsp" style=""></span>mg twice a day for five days&#46;</p></li><li class="elsevierStyleListItem" id="lsti0095"><span class="elsevierStyleLabel">-</span><p id="par0215" class="elsevierStylePara elsevierViewall">Valaciclovir 500<span class="elsevierStyleHsp" style=""></span>mg a day &#40;if fewer than 10 recurrences&#47;year&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0100"><span class="elsevierStyleLabel">-</span><p id="par0220" class="elsevierStylePara elsevierViewall">Valaciclovir 1<span class="elsevierStyleHsp" style=""></span>g a day &#40;more than 10 recurrences&#47;year&#41;&#46;</p></li></ul></p><p id="par0225" class="elsevierStylePara elsevierViewall">Recent studies indicate that topical microbicides&#44; such as the 1&#37; tenofovir or 3&#37; SPL7013 gels&#44; may be a promising option&#44; having achieved a 51&#37; reduction in the risk of HSV-2 infection&#46;<a class="elsevierStyleCrossRefs" href="#bib0380"><span class="elsevierStyleSup">33&#44;34</span></a> Another alternative is helicase-primase inhibitors&#44; such as ASP2151&#44; for the treatment of recurrent genital herpes&#46;<a class="elsevierStyleCrossRefs" href="#bib0390"><span class="elsevierStyleSup">35&#44;36</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">Therapeutic vaccines are another potential strategy for the management of HSV-positive patients&#44; but few of the earlier trials obtained optimal results&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">32</span></a> New trials focused on the immune response of the host&#44; through the use of HSV peptides &#40;HerpV&#41;&#44; have achieved promising results in phase I and are now in phase I&#47;IIa&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">37&#8211;40</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">Prophylactic vaccines have been under continuous development and improvement for years&#44; prominent among which are two containing the HSV-2 glycoprotein D subunit&#44; with a demonstrated efficacy of 73&#8211;74&#37; among women seronegative for both types of HSV&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">41</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Analysis of health service costs related to HSV disease</span><p id="par0240" class="elsevierStylePara elsevierViewall">A recently published study<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">42</span></a> calculated the costs associated with HSV infection in hospital accident and emergency units&#46; In the period 2006&#8211;2013 the cost amounted to 543 million dollars&#44; going from 45 million dollars in 2006 to 91 million in 2013&#44; primarily due to a 24&#37; increase in the number of patients&#46; The study emphasises the need for continuous prevention and patient sex education to avoid new cases&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Level of evidence</span><p id="par0245" class="elsevierStylePara elsevierViewall">For more information and details about levels of evidence and grades of recommendation see&#58; <a id="intr0010" class="elsevierStyleInterRef" href="http://www.iusti.org/regions/Europe/pdf/2013/Levels_of_Evidence.pdf">http&#58;&#47;&#47;www&#46;iusti&#46;org&#47;regions&#47;Europe&#47;pdf&#47;2013&#47;Levels&#95;of&#95;Evidence&#46;pdf</a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of interest</span><p id="par0250" class="elsevierStylePara elsevierViewall">The author declares that there are no conflicts of interest regarding the research&#44; authorship&#44; and&#47;or publication of this literature review&#46;</p></span></span>"
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            0 => "Vaginitis"
            1 => "&#218;lceras genitales"
            2 => "Virus herpes simplex"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Genital herpes is a sexually transmitted disease caused by herpes simplex virus type 1 &#40;HSV-1&#41; and type 2 &#40;HSV-2&#41; belonging to the alphaherpesvirus family&#44; that includes the varicella zoster virus&#46; HSV infection continues to be the most common cause of vulvar ulcers among the sexually active population&#46; Its incidence increases every year&#46; This review summarises the microbiology of the virus&#44; pathogenesis and infection in genitalia&#44; clinical manifestations and correct identification&#44; the different laboratory diagnostic methods&#44; and choice of the correct treatment according to the first infection&#44; recurrence or special cases&#46; Finally&#44; the cost of routine herpes simplex virus infection is analysed&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">El herpes genital es una enfermedad de transmisi&#243;n sexual causada por los virus herpes simplex tipo 1 &#40;VHS-1&#41; y tipo 2 &#40;VHS-2&#41;&#44; pertenecientes&#44; junto al virus varicela zoster&#44; a la familia alfaherpesviridae&#46; La lesi&#243;n por VHS contin&#250;a siendo la causa m&#225;s frecuente de &#250;lcera vulvar entre la poblaci&#243;n sexualmente activa&#44; y su incidencia aumenta cada a&#241;o&#46; En esta revisi&#243;n resumiremos la microbiolog&#237;a del virus&#44; la patogenia y la infecci&#243;n en genitales&#44; las manifestaciones cl&#237;nicas para su correcta identificaci&#243;n&#44; las diferentes t&#233;cnicas diagn&#243;sticas de laboratorio y la elecci&#243;n del correcto tratamiento seg&#250;n sea primera infecci&#243;n&#44; recurrencia o casos especiales&#46; Finalmente&#44; se discute un an&#225;lisis de costes de la enfermedad por VHS&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Parra-S&#225;nchez M&#46; &#218;lceras genitales por virus herpes simplex&#46; Enferm Infecc Microbiol Clin&#46; 2019&#59;37&#58;260&#8211;264&#46;</p>"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Viral and cellular contributions to herpes simplex virus entry into the cell"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "G&#46; Campadelli-Fiume"
                            1 => "L&#46; Menotti"
                            2 => "E&#46; Avitabile"
                            3 => "T&#46; Gianni"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.coviro.2011.12.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Virol"
                        "fecha" => "2012"
                        "volumen" => "2"
                        "paginaInicial" => "28"
                        "paginaFinal" => "36"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22440963"
                            "web" => "Medline"
                          ]
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                ]
              ]
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            1 => array:3 [
              "identificador" => "bib0225"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Epidemiology&#44; clinical presentation&#44; and antibody response to primary infection with herpes simplex virus type 1 and type 2 in young women"
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                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "D&#46;I&#46; Bernstein"
                            1 => "A&#46;R&#46; Bellamy"
                            2 => "E&#46;W&#46; Hook"
                            3 => "M&#46;J&#46; Levin"
                            4 => "A&#46; Wald"
                            5 => "M&#46;G&#46; Ewell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/cid/cis891"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Infect Dis"
                        "fecha" => "2013"
                        "volumen" => "56"
                        "paginaInicial" => "344"
                        "paginaFinal" => "351"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23087395"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Topics in herpesvirus genomics and evolution"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "D&#46;J&#46; McGeoch"
                            1 => "F&#46;J&#46; Rixon"
                            2 => "A&#46;J&#46; Davison"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.virusres.2006.01.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "Virus Res"
                        "fecha" => "2006"
                        "volumen" => "117"
                        "paginaInicial" => "90"
                        "paginaFinal" => "104"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16490275"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Increasing role of herpes simplex virus type 1 in first episode anogenital herpes in heterosexual women and younger men who have sex with men&#44; 1992&#8211;2006"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "N&#46; Ryder"
                            1 => "F&#46; Jin"
                            2 => "A&#46;M&#46; McNulty"
                            3 => "A&#46;E&#46; Grulich"
                            4 => "B&#46; Donovan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/sti.2008.033902"
                      "Revista" => array:6 [
                        "tituloSerie" => "Sex Transm Infect"
                        "fecha" => "2009"
                        "volumen" => "85"
                        "paginaInicial" => "416"
                        "paginaFinal" => "419"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19273479"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0240"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Prevalence of herpes simplex virus type 1 and type 2 in persons aged 14&#8211;49&#58; United States&#44; 2015&#8211;2016"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "G&#46; McQuillan"
                            1 => "D&#46; Kruszon-Moran"
                            2 => "E&#46;W&#46; Flagg"
                            3 => "R&#46; Paulose-Ram"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "NCHS Data Brief"
                        "fecha" => "2018"
                        "volumen" => "304"
                        "paginaInicial" => "1"
                        "paginaFinal" => "8"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0245"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Global and regional estimates of prevalent and incident herpes simplex virus type 1 infections in 2012"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;J&#46; Looker"
                            1 => "A&#46;S&#46; Magaret"
                            2 => "M&#46;T&#46; May"
                            3 => "K&#46;M&#46;E&#46; Turner"
                            4 => "P&#46; Vickerman"
                            5 => "S&#46;L&#46; Gottlieb"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "PLOS ONE"
                        "fecha" => "2015"
                        "volumen" => "10"
                        "paginaInicial" => "1"
                        "paginaFinal" => "17"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0250"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:3 [
                  "comentario" => "Available from&#58; <a class="elsevierStyleInterRef" target="_blank" id="intr0015" href="https://www.ncbi.nlm.nih.gov/books/NBK396232/">https&#58;&#47;&#47;www&#46;ncbi&#46;nlm&#46;nih&#46;gov&#47;books&#47;NBK396232&#47;</a> &#91;accessed 01&#46;09&#46;18&#93;"
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "WHO guidelines for the treatment of genital herpes simplex virus"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2016"
                        "editorial" => "World Health Organization"
                        "editorialLocalizacion" => "Geneva"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0255"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Herpes simplex virus&#58; the interplay between HSV&#44; host&#44; and HIV-1"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46;V&#46; Desai"
                            1 => "S&#46;S&#46; Kulkarni"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1089/vim.2015.0012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Viral Immunol"
                        "fecha" => "2015"
                        "volumen" => "28"
                        "paginaInicial" => "546"
                        "paginaFinal" => "555"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26331265"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0260"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genital herpes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46; Gupta"
                            1 => "T&#46; Warren"
                            2 => "A&#46; Wald"
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                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(07)61908-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet"
                        "fecha" => "2007"
                        "volumen" => "370"
                        "paginaInicial" => "2127"
                        "paginaFinal" => "2137"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18156035"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0265"
              "etiqueta" => "10"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "AEPCC-Gu&#237;a&#58; Infecciones del tracto genital inferior"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Alsina"
                            1 => "O&#46; Arencibia"
                            2 => "C&#46; Centeno"
                            3 => "P&#46; de la Cueva"
                            4 => "I&#46; Fuertes"
                            5 => "P&#46; Fust&#233;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
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                        "fecha" => "2016"
                        "paginaInicial" => "1"
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                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0270"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "An inquiry into the molecular basis of HSV latency and reactivation"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "B&#46; Roizman"
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                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1146/annurev-micro-092412-155654"
                      "Revista" => array:6 [
                        "tituloSerie" => "Annu Rev Microbiol"
                        "fecha" => "2013"
                        "volumen" => "67"
                        "paginaInicial" => "355"
                        "paginaFinal" => "374"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24024635"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "F&#46; Xu"
                            1 => "M&#46;R&#46; Sternberg"
                            2 => "B&#46;J&#46; Kottiri"
                            3 => "G&#46;M&#46; McQuillan"
                            4 => "F&#46;K&#46; Lee"
                            5 => "A&#46;J&#46; Nahmias"
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                        ]
                      ]
                    ]
                  ]
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                    0 => array:2 [
                      "doi" => "10.1001/jama.296.8.964"
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                        "tituloSerie" => "JAMA"
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                        "volumen" => "296"
                        "paginaInicial" => "964"
                        "paginaFinal" => "973"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16926356"
                            "web" => "Medline"
                          ]
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                      ]
                    ]
                  ]
                ]
              ]
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              "identificador" => "bib0280"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Genital herpes"
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                          "etal" => false
                          "autores" => array:2 [
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                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.bpobgyn.2014.07.015"
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                        "tituloSerie" => "Best Pract Res Clin Obstet Gynaecol"
                        "fecha" => "2014"
                        "volumen" => "28"
                        "paginaInicial" => "1098"
                        "paginaFinal" => "1110"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25153069"
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                  ]
                ]
              ]
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                0 => array:2 [
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                      "titulo" => "Optimal management of genital herpes&#58; current perspectives"
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                          "etal" => false
                          "autores" => array:1 [
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2147/IDR.S96164"
                      "Revista" => array:6 [
                        "tituloSerie" => "Infect Drug Resist"
                        "fecha" => "2016"
                        "volumen" => "9"
                        "paginaInicial" => "129"
                        "paginaFinal" => "141"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27358569"
                            "web" => "Medline"
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                      ]
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                ]
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                    0 => array:2 [
                      "titulo" => "Clinical practice&#46; Genital herpes"
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                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2004"
                        "volumen" => "350"
                        "paginaInicial" => "1970"
                        "paginaFinal" => "1977"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15128897"
                            "web" => "Medline"
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                ]
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                    0 => array:2 [
                      "titulo" => "The value of Tzanck smear test in diagnosis of erosive&#44; vesicular&#44; bullous&#44; and pustular skin lesions"
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                        0 => array:2 [
                          "etal" => false
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                    ]
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                    0 => array:2 [
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                        "tituloSerie" => "J Am Acad Dermatol"
                        "fecha" => "2008"
                        "volumen" => "59"
                        "paginaInicial" => "958"
                        "paginaFinal" => "964"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18929431"
                            "web" => "Medline"
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                    ]
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                ]
              ]
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                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Herpes simplex virus detection from genital lesions&#58; a comparative study using antigen detection &#40;HerpChek&#41; and culture"
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                        0 => array:2 [
                          "etal" => false
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                            4 => "L&#46; Corey"
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                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Microbiol"
                        "fecha" => "1993"
                        "volumen" => "31"
                        "paginaInicial" => "1774"
                        "paginaFinal" => "1776"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8394375"
                            "web" => "Medline"
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                      ]
                    ]
                  ]
                ]
              ]
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                            2 => "M&#46;D&#46; Poulter"
                            3 => "Y&#46;W&#46; Tang"
                            4 => "P&#46;A&#46; Granato"
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                      ]
                    ]
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                        "paginaInicial" => "355"
                        "paginaFinal" => "358"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22613012"
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                  ]
                ]
              ]
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                0 => array:2 [
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                      "titulo" => "Detection of type-specific antibodies to HSV-1 and HSV-2&#58; comparative analysis of a chemiluminescence immunoassay with a conventional ELISA"
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                          "autores" => array:5 [
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                            3 => "G&#46; Schwichtenberg"
                            4 => "B&#46; Detrick"
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                    0 => array:2 [
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                        "tituloSerie" => "Diagn Microbiol Infect Dis"
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                        "paginaInicial" => "273"
                        "paginaFinal" => "274"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22534561"
                            "web" => "Medline"
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                ]
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of commercial methods of immunoblot ELISA&#44; and chemiluminescent immunoassay for detecting type-specific herpes simplex viruses-1 and -2 IgG"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "F&#46; De Ory"
                            1 => "M&#46;E&#46; Guisasola"
                            2 => "P&#46; Balfag&#243;n"
                            3 => "J&#46;C&#46; Sanz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "J Clin Lab Anal"
                        "fecha" => "2018"
                        "volumen" => "32"
                        "paginaInicial" => "e22203"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0320"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development of a time-resolved fluorescence immunoassay for herpes simplex virus type 1 and type 2 IgG antibodies"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Q&#46;N&#46; Liang"
                            1 => "J&#46;W&#46; Zhou"
                            2 => "T&#46;C&#46; Liu"
                            3 => "G&#46;F&#46; Lin"
                            4 => "Z&#46;N&#46; Dong"
                            5 => "Z&#46;H&#46; Chen"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/bio.2800"
                      "Revista" => array:6 [
                        "tituloSerie" => "Luminescence"
                        "fecha" => "2015"
                        "volumen" => "30"
                        "paginaInicial" => "649"
                        "paginaFinal" => "654"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25377426"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0325"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation of commercial herpes simplex virus IgG and IgM enzyme immunoassays"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "K&#46; Liermann"
                            1 => "A&#46; Sch&#228;fler"
                            2 => "A&#46; Henke"
                            3 => "A&#46; Sauerbrei"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jviromet.2014.01.001"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Virol Methods"
                        "fecha" => "2014"
                        "volumen" => "199"
                        "paginaInicial" => "29"
                        "paginaFinal" => "34"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24418499"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0330"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Performance of commercial enzyme-linked immunoassays for diagnosis of herpes simplex virus-1 and herpes simplex virus-2 infection in a clinical setting"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "E&#46; Agyemang"
                            1 => "Q&#46;A&#46; Le"
                            2 => "T&#46; Warren"
                            3 => "A&#46;S&#46; Magaret"
                            4 => "S&#46; Selke"
                            5 => "C&#46; Johnston"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/OLQ.0000000000000689"
                      "Revista" => array:6 [
                        "tituloSerie" => "Sex Transm Dis"
                        "fecha" => "2017"
                        "volumen" => "44"
                        "paginaInicial" => "763"
                        "paginaFinal" => "767"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28876290"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0335"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serological testing for herpes simplex virus &#40;HSV&#41;-1 and HSV-2 infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "A&#46; Wald"
                            1 => "R&#46; Ashley-Morrow"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1086/342104"
                      "Revista" => array:7 [
                        "tituloSerie" => "Clin Infect Dis"
                        "fecha" => "2002"
                        "volumen" => "35"
                        "numero" => "Suppl&#46; 2"
                        "paginaInicial" => "S173"
                        "paginaFinal" => "S182"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12353203"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0340"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serological profile of HSV-2 in STD patients&#58; evaluation of diagnostic utility of HSV-2 IgM and IgG detection"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "V&#46;P&#46; Amudha"
                            1 => "Rashetha"
                            2 => "G&#46; Sucilathangam"
                            3 => "B&#46; Cinthujah"
                            4 => "C&#46; Revathy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7860/JCDR/2014/10586.5314"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Diagn Res"
                        "fecha" => "2014"
                        "volumen" => "8"
                        "paginaInicial" => "DC16"
                        "paginaFinal" => "DC19"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25653947"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
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            25 => array:3 [
              "identificador" => "bib0345"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serologic screening for genital herpes&#58; an updated evidence report and systematic review for the US Preventive Services Task Force"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Feltner"
                            1 => "C&#46; Grodensky"
                            2 => "C&#46; Ebel"
                            3 => "J&#46;C&#46; Middleton"
                            4 => "R&#46;P&#46; Harris"
                            5 => "M&#46; Ashok"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.2016.17138"
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                        "tituloSerie" => "JAMA"
                        "fecha" => "2016"
                        "volumen" => "316"
                        "paginaInicial" => "2531"
                        "paginaFinal" => "2543"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27997660"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0350"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnostics for herpes simplex virus&#58; is PCR the new gold standard&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "L&#46;B&#46; Strick"
                            1 => "A&#46; Wald"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/BF03256439"
                      "Revista" => array:6 [
                        "tituloSerie" => "Mol Diagn Ther"
                        "fecha" => "2006"
                        "volumen" => "10"
                        "paginaInicial" => "17"
                        "paginaFinal" => "28"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16646574"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0355"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Diagnosis of genital herpes by real time PCR in routine clinical practice"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46; Ramaswamy"
                            1 => "C&#46; McDonald"
                            2 => "M&#46; Smith"
                            3 => "D&#46; Thomas"
                            4 => "S&#46; Maxwell"
                            5 => "M&#46; Tenant-Flowers"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1136/sti.2003.008201"
                      "Revista" => array:6 [
                        "tituloSerie" => "Sex Transm Infect"
                        "fecha" => "2004"
                        "volumen" => "80"
                        "paginaInicial" => "406"
                        "paginaFinal" => "410"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15459412"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0360"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Automated processing&#44; extraction and detection of herpes simplex virus types 1 and 2&#58; a comparative evaluation of three commercial platforms using clinical specimens"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46;J&#46; Binnicker"
                            1 => "M&#46;J&#46; Espy"
                            2 => "B&#46; Duresko"
                            3 => "C&#46; Irish"
                            4 => "J&#46; Mandrekar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jcv.2017.02.006"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Virol"
                        "fecha" => "2017"
                        "volumen" => "89"
                        "paginaInicial" => "30"
                        "paginaFinal" => "33"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28226272"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0365"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A European multi-centre External Quality Assessment &#40;EQA&#41; study on phenotypic and genotypic methods used for Herpes Simplex Virus &#40;HSV&#41; drug resistance testing"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "B&#46; Afshar"
                            1 => "D&#46;F&#46; Bibby"
                            2 => "R&#46; Piorkowska"
                            3 => "N&#46; Ohemeng-Kumi"
                            4 => "R&#46; Snoeck"
                            5 => "G&#46; Andrei"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jcv.2017.10.002"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Virol"
                        "fecha" => "2017"
                        "volumen" => "96"
                        "paginaInicial" => "89"
                        "paginaFinal" => "93"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29031157"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            30 => array:3 [
              "identificador" => "bib0370"
              "etiqueta" => "31"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "2017 European guidelines for the management of genital herpes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Patel"
                            1 => "O&#46;J&#46; Kennedy"
                            2 => "E&#46; Clarke"
                            3 => "A&#46; Geretti"
                            4 => "A&#46; Nilsen"
                            5 => "S&#46; Lautenschlager"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1177/0956462417727194"
                      "Revista" => array:6 [
                        "tituloSerie" => "Int J STD AIDS"
                        "fecha" => "2017"
                        "volumen" => "28"
                        "paginaInicial" => "1366"
                        "paginaFinal" => "1379"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28836892"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            31 => array:3 [
              "identificador" => "bib0375"
              "etiqueta" => "32"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Current thinking on genital herpes"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;M&#46; Hofstetter"
                            1 => "S&#46;L&#46; Rosenthal"
                            2 => "L&#46;R&#46; Stanberry"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/QCO.0000000000000029"
                      "Revista" => array:6 [
                        "tituloSerie" => "Curr Opin Infect Dis"
                        "fecha" => "2014"
                        "volumen" => "27"
                        "paginaInicial" => "75"
                        "paginaFinal" => "83"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24335720"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            32 => array:3 [
              "identificador" => "bib0380"
              "etiqueta" => "33"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effectiveness and safety of tenofovir gel&#44; an antiretroviral microbicide&#44; for the prevention of HIV infection in women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "Q&#46; Abdool Karim"
                            1 => "S&#46;S&#46; Abdool Karim"
                            2 => "J&#46;A&#46; Frohlich"
                            3 => "A&#46;C&#46; Grobler"
                            4 => "C&#46; Baxter"
                            5 => "L&#46;E&#46; Mansoor"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1126/science.1193748"
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                        "tituloSerie" => "Science"
                        "fecha" => "2010"
                        "volumen" => "329"
                        "paginaInicial" => "1168"
                        "paginaFinal" => "1174"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20643915"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            33 => array:3 [
              "identificador" => "bib0385"
              "etiqueta" => "34"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A phase I randomized placebo controlled trial of the safety of 3&#37; SPL7013 Gel &#40;VivaGel<span class="elsevierStyleSup">&#174;</span>&#41; in healthy young women administered twice daily for 14 days"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
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                            1 => "J&#46; Brown"
                            2 => "A&#46;B&#46; Moscicki"
                            3 => "E&#46;A&#46; Bukusi"
                            4 => "J&#46;R&#46; Paull"
                            5 => "C&#46;F&#46; Price"
                          ]
                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1371/journal.pone.0016258"
                      "Revista" => array:5 [
                        "tituloSerie" => "PLoS ONE"
                        "fecha" => "2011"
                        "volumen" => "6"
                        "paginaInicial" => "e16258"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21311578"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            34 => array:3 [
              "identificador" => "bib0390"
              "etiqueta" => "35"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Recent developments in antiherpesvirus drugs"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "H&#46;J&#46; Field"
                            1 => "R&#46;A&#46; Vere Hodge"
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                        ]
                      ]
                    ]
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                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/bmb/ldt011"
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                        "tituloSerie" => "Br Med Bull"
                        "fecha" => "2013"
                        "volumen" => "106"
                        "paginaInicial" => "213"
                        "paginaFinal" => "249"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23596085"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
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              "identificador" => "bib0395"
              "etiqueta" => "36"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "ASP2151 for the treatment of genital herpes&#58; a randomized&#44; double-blind&#44; placebo- and valacyclovir-controlled&#44; dose-finding study"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Tyring"
                            1 => "A&#46; Wald"
                            2 => "N&#46; Zadeikis"
                            3 => "S&#46; Dhadda"
                            4 => "K&#46; Takenouchi"
                            5 => "R&#46; Rorig"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/infdis/jis019"
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                        "tituloSerie" => "J Infect Dis"
                        "fecha" => "2012"
                        "volumen" => "205"
                        "paginaInicial" => "1100"
                        "paginaFinal" => "1110"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22351940"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            36 => array:3 [
              "identificador" => "bib0400"
              "etiqueta" => "37"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A heat shock protein based polyvalent vaccine targeting HSV-2&#58; CD4&#40;&#43;&#41; and CD8&#40;&#43;&#41; cellular immunity and protective efficacy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; Mo"
                            1 => "C&#46; Musselli"
                            2 => "H&#46; Chen"
                            3 => "J&#46; Pappas"
                            4 => "K&#46; Leclair"
                            5 => "A&#46; Liu"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.vaccine.2011.07.011"
                      "Revista" => array:6 [
                        "tituloSerie" => "Vaccine"
                        "fecha" => "2011"
                        "volumen" => "29"
                        "paginaInicial" => "8530"
                        "paginaFinal" => "8541"
                        "link" => array:1 [
                          0 => array:2 [
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                      "titulo" => "Safety and immunogenicity of long HSV-2 peptides complexed with rhHsc70 in HSV-2 seropositive persons"
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                          "etal" => true
                          "autores" => array:6 [
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                            4 => "K&#46; Leclair"
                            5 => "R&#46;M&#46; Chicz"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.vaccine.2011.09.046"
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                        "tituloSerie" => "Vaccine"
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                        "volumen" => "29"
                        "paginaInicial" => "8520"
                        "paginaFinal" => "8529"
                        "link" => array:1 [
                          0 => array:2 [
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                ]
              ]
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              "etiqueta" => "39"
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              "etiqueta" => "41"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Efficacy results of a trial of a herpes simplex vaccine"
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                        0 => array:2 [
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                          "autores" => array:6 [
                            0 => "R&#46;B&#46; Belshe"
                            1 => "P&#46;A&#46; Leone"
                            2 => "D&#46;I&#46; Bernstein"
                            3 => "A&#46; Wald"
                            4 => "M&#46;J&#46; Levin"
                            5 => "J&#46;T&#46; Stapleton"
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                        "fecha" => "2012"
                        "volumen" => "366"
                        "paginaInicial" => "34"
                        "paginaFinal" => "43"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22216840"
                            "web" => "Medline"
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                ]
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              "identificador" => "bib0425"
              "etiqueta" => "42"
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                    0 => array:2 [
                      "titulo" => "Cost of routine herpes simplex virus infection visits to U&#46;S Emergency Departments 2006&#8211;2013"
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                          "etal" => false
                          "autores" => array:5 [
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                            2 => "E&#46; Dommasch"
                            3 => "C&#46; Joyce"
                            4 => "A&#46; Mostaghimi"
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                        "tituloSerie" => "West J Emerg Med"
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                        "volumen" => "19"
                        "paginaInicial" => "689"
                        "paginaFinal" => "692"
                        "link" => array:1 [
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                ]
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                        "tituloSerie" => "Microb Cell"
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Article information

ISSN: 2529993X
Original language: English

DOI:10.1016/j.eimce.2019.01.001

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Year/Month	Html	Pdf	Total

2024 November	28	7	35
2024 October	264	65	329
2024 September	343	53	396
2024 August	385	39	424
2024 July	366	38	404
2024 June	299	27	326
2024 May	327	30	357
2024 April	349	33	382
2024 March	520	36	556
2024 February	623	50	673
2024 January	822	40	862
2023 December	523	72	595
2023 November	573	73	646
2023 October	565	68	633
2023 September	526	49	575
2023 August	576	70	646
2023 July	602	56	658
2023 June	750	65	815
2023 May	721	51	772
2023 April	617	55	672
2023 March	605	72	677
2023 February	506	37	543
2023 January	503	82	585
2022 December	471	54	525
2022 November	583	52	635
2022 October	549	46	595
2022 September	497	54	551
2022 August	545	53	598
2022 July	422	70	492
2022 June	406	34	440
2022 May	284	29	313
2022 April	370	32	402
2022 March	433	56	489
2022 February	546	45	591
2022 January	342	21	363
2021 December	293	29	322
2021 November	309	24	333
2021 October	340	31	371
2021 September	317	25	342
2021 August	353	26	379
2021 July	379	23	402
2021 June	309	8	317
2021 May	376	40	416
2021 April	959	38	997
2021 March	445	25	470
2021 February	341	23	364
2021 January	325	23	348
2020 December	296	21	317
2020 November	250	34	284
2020 October	170	14	184
2020 September	200	26	226
2020 August	178	14	192
2020 July	169	15	184
2020 June	175	12	187
2020 May	142	15	157
2020 April	90	8	98
2020 March	129	9	138
2020 February	73	3	76
2020 January	52	6	58
2019 December	16	5	21
2019 November	13	4	17
2019 October	13	6	19
2019 September	1	0	1
2019 April	4	4	8
2019 March	4	0	4

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