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Signs herpes outbreak is coming

Expression of concern regarding paper by Park et al, published on 25 June 2015: “Epidemiological investigation of MERS-CoV spread in a single hospital in South Korea, May to June 2015”, Euro Surveill.
It has been brought to our attention that some of the authors may not have been informed about the content of the above paper. Citation style for this article: Domeika M, Bashmakova M, Savicheva A, Kolomiec N, Sokolovskiy E, Hallen A, Unemo M, Ballard RC, Eastern European Network for Sexual and Reproductive Health (EE SRH Network). These guidelines aim to provide comprehensive information about sexually transmitted herpes simplex virus (HSV) infection and its laboratory diagnosis in eastern European countries. During the past 20 years, genital herpes has emerged as one of the most prevalent sexually transmitted infections (STIs).
The clinical differentiation of genital HSV infection from other infectious and non-infectious aetiologies of genital ulceration is difficult and laboratory confirmation of the infection should always be sought [5,9]. The guidelines presented here represent the first attempt to introduce an evidence-based approach to the laboratory diagnosis of genital herpes infections in eastern Europe. Laboratory confirmation of the clinical diagnosis is necessary for estimating the potential infectivity during episodes of lesions, identifying persons at risk of transmitting infection subclinically, selecting women at future risk of transmitting the infection to the neonate and confirming the clinical diagnosis in those for whom antiviral therapy for HIV infection should be prescribed [8]. Methods used for the diagnosis of HSV could be divided into direct detection of virus in material from lesions and serological diagnosis.
The recommended sampling sites and type of sample and methods to be used for the diagnosis of genital herpes infection are presented in Table 4. The recommendations for sample transportation for testing using microscopy, culture and NAATs are presented in Table 5.
The recommended sites and methods to be used for the diagnosis of genital herpes infection are presented in Table 6.
Microscopic examination of lesion materials using Romanovsky staining is used by a number of laboratories in Eastern Europe [17].
Viral antigen from swab specimens can be detected using either direct immunofluorescence (DIF) or enzyme immunoassay (EIA). DIF could be classified as a rapid diagnostic test allowing type differentiation of genital herpes viruses [19,20].
The sensitivity of commercially available EIAs, when compared with that of viral isolation, is greater than or equal to 95% and with specificities ranging from 62% to 100% for symptomatic patients [22-27]. Virus isolation in cell culture has been the cornerstone of HSV diagnosis over the past two decades in laboratories of western Europe [28,29] and the United States [30]. Virus isolation in tissue culture roller tubes is slow and labour intensive, but has the advantage of demonstrating active infection within a clinical lesion and also allows virus typing and antiviral sensitivity testing [32]. Typing of HSV using cell culture can be performed directly on infected cell cultures using fluorescein isothiocyanate (FITC)- or immunoperoxidase-labelled type-specific monoclonal antibodies by DIF or by testing the cell supernatant by nucleic acid amplification tests (NAATs), with specifically designed primers.
HSV detection using polymerase chain reaction (PCR) has been shown to be the test of choice in patients with genital herpes ulcers. As in western Europe and the United States, there are no comprehensively validated and approved commercial NAATs available for detection of HSV in many eastern European countries. In each DNA extraction and subsequent analysis, an internal positive control – allowing detection of amplification-inhibited samples and controlling the quality of sample preparation – and a negative control are necessary.
Certified and registered reference panels comprising coded control specimens should ideally be used for intra- and inter-laboratory quality control.
Serological tests detect antibodies to HSV in blood, which are indicative of ongoing latent infection.
General criteria for the validation of diagnostic tests have been published by the TDR diagnostics evaluation expert panel (TDR is a Special Programme for Research and Training in Tropical Diseases, sponsored by the United Nations Children's Fund (UNICEF), the United Nations Development Programme (UNDP), the World Bank and WHO [44]. Older, classical tests can display cross-reactivity between HSV-1 and HSV-2 and even with varicella-zoster virus. Where viral culture facilities exist, they should be maintained in order to detect the causative virus directly from skin and mucous membrane lesions. These guidelines were written on behalf of the STI Diagnostic Group of the EE SRH Network, which is supported by grants from the East Europe Committee of the Swedish Health Care Community, Swedish International Development Cooperation Agency (SIDA).
Domeika M, Savicheva A, Sokolovskiy E, Ballard R, Unemo M; Eastern European Network for Sexual and Reproductive Health (EE SRH Network). Disclaimer: The opinions expressed by authors contributing to Eurosurveillance do not necessarily reflect the opinions of the European Centre for Disease Prevention and Control (ECDC) or the editorial team or the institutions with which the authors are affiliated. As their name says, sexually transmitted diseases (STDs) refer to illnesses that are usually transmitted through sexual contact. Generally speaking, not all illnesses that can be transmitted through sexual contact are classified as STDs.
Viral STDs are caused by viruses and are the most notorious category, including HIV, Viral hepatitis (B or C), Herpes (oral or genital), HPV or Molluscum contagiosum.
Primarily, STDs are being transmitted through the exchange of saliva, venereal fluids, skin or mucosal contact; however, sweat, urine and feces can also transmit such infections. In cases such as herpes, the infection becomes much more contagious once it has developed in a disease – since the blisters ease the body fluid exchange. While the risk of infection can never be entirely eliminated, when having intercourse with an infected person, it is strongly diminished if safe sex is practiced (mainly through the use of condoms). Because of the use of needles, drug users and medical workers are occasionally considered at high risk of contracting the diseases (through ways other than sexually) and they are recommended to get tested on a regular basis.
It is statistically proven that the more sexual partners you have, the more likely you are to contract an STD – especially in the case of random intercourse. Since it is often the case that an infection may be prezent in your body without actually showing symptoms, regular check-ups (especially in the case of an active sexual life that does not include a stable partner) and going for STD testing are very important in preventing and diagnosing STDs. Even in the case of asymptomatic infections, the lack of treatment may in a long time lead to effects like severe chronic pain, infertility and death.
Since, in the case of most STDs, tests do not detect the illness immediately after it has been contracted, it is recommended to continue with the testing even in the case of a break in sexual activity. If you suspect that you might have an STD, you should visit a physician or STD testing clinic immediately.  In all likelihood, there are several STD Test Clinics in your area.
While underdeveloped countries have a considerably higher infection rate, STDs continue to cause numerous infections in the entire world. In developing countries, STDs are in the top five most contracted diseases and, even excluding HIV,  are the second most likely cause of disease and death. A Differential Diagnosis of the Swollen Red EyelidA  This is a corrected version of the article that appeared in print. Depending on tumor type, Mohs micrographic surgery or wide local excision*— Alternative empiric regimens may be necessary in patients with community-acquired methicillin-resistant Staphylococcus aureus cellulitis.
Herpes simplex encephalitis (HSE) is the most common sporadic focal encephalitis produced by Herpes simplex virus type I. HSE manifests with classical features of acute focal encephalitis and rarely may have a chronic smouldering course. Send Home Our method Usage examples Index Contact StatisticsWe do not evaluate or guarantee the accuracy of any content in this site. Use of images for any purpose including but not limited to research, commercial, personal, or non-commercial use is prohibited without prior written consent. They are primarily intended for professionals testing specimens from patients at a sexual healthcare clinic but may also be helpful for community-based screening programmes. However, data on morbidity due to genital herpes infections in eastern European countries is scarce and their reliability doubtful owing to the lack of validation studies for the diagnostic tests used. In general, infections caused by HSV-1 manifest above the neck and are acquired as a result of close contact with infected persons, usually in childhood.
The recurrences arise with different frequency: from once every few years to several times per month. Neonatal herpes (including neonatal encephalitis) and increased risk for acquiring and shedding human immunodeficiency virus (HIV) are the most serious consequences of genital herpes infection [8,9].
Accordingly, exclusive reliance on clinical diagnosis could lead both to false positive and false negative diagnosis of the condition [6,9]. It is recognised that national adjustments to these guidelines may be needed in some eastern European countries to meet local laws and health strategies and according to the availability of kits and reagents. Both virological detection and type-specific serological tests for HSV should be available in clinical settings that provide care for patients with STIs or those at risk for STIs. This method, however, as well as cytological examination using Tzanckand Papanicolaou smears, have been found to have low sensitivity and specificity, and therefore should not be relied upon for diagnosis [5,9,18]. Commercial diagnostic tests produced in eastern European countries for the detection of herpes-specific virus antigen have not been validated against any international standard test; therefore the data presented below reflect characteristics of tests produced in western countries. It can be valuable when testing high-prevalence populations [21], but when testing asymptomatic patients, the sensitivity may drop to less than 50% when compared with culture [19,21].
The sensitivity of antigen capture EIAs may be higher than that of virus culture for typical presentations, but lower for cervical and urethral swabs [22-24,27].
Although HSV can be isolated from over 90% of vesicular or pustular lesions, the isolation rate from ulcerative lesions is only 70% and falls to 27% at the crusting stage [4]. More rapid culture of HSV can be achieved by using shell vials [33] or multiwell plates [34] and centrifuging the specimen onto cell monolayers on coverslips.


The detection rates of the PCR assays were shown to be 11–71% superior to virus culture [30,31,37-39]. However, some NAATs for HSV detection have been developed and are available in eastern Europe, but have not been validated against their internationally acknowledged analogues. Both type- and non-type-specific antibodies to HSV develop during the first several weeks after infection and persist indefinitely. During the past 20 years, a number of type-specific tests have been developed, the sensitivity and specificity of which have been evaluated to be approximately 97% and 98%, respectively [46]. Where culture is not available, consideration should be given to the introduction of a NAAT for HSV. An estimate of the global prevalence and incidence of herpes simplex virus type 2 infection. Genital herpes simplex virus infections: clinical manifestations, course, and complications. Genital herpes simplex virus infections: current concepts in diagnosis, therapy, and prevention. Reactivation of genital herpes simplex virus type 2 infection in asymptomatic seropositive persons.
Risk of human immunodeficiency virus infection in herpes simplex virus type 2-seropositive persons: a meta-analysis. Guidelines for laboratory diagnosis of Neisseria gonorrhoeae infections in Eastern European countries--results of an international collaboration. Quality enhancements and quality assurance of laboratory diagnosis of sexually transmitted infections in Eastern Europe.
Guidelines for the laboratory diagnosis of Chlamydia trachomatis infections in East European countries. Comparison of viral isolation, direct immunofluorescence, and indirect immunoperoxidase techniques for detection of genital herpes simplex virus infection. Antibody and interferon act synergistically to inhibit enterovirus, adenovirus, and herpes simplex virus infection.
Diagnosis of herpes simplex virus by direct immunofluorescence and viral isolation from samples of external genital lesions in a high-prevalence population. Evaluation of a commercial enzyme-linked immunosorbent assay for detection of herpes simplex virus antigen. A comparison of PCR with virus isolation and direct antigen detection for diagnosis and typing of genital herpes. Comparison of Light-Cycler PCR, enzyme immunoassay, and tissue culture for detection of herpes simplex virus.
Detection and subtyping of Herpes simplex virus in clinical samples by LightCycler PCR, enzyme immunoassay and cell culture. Rapid detection, culture-amplification and typing of herpes simplex viruses by enzyme immunoassay in clinical samples. Comparison of two enzyme-linked immunosorbent assays for detection of herpes simplex virus antigen. Herpes simplex virus detection from genital lesions: a comparative study using antigen detection (HerpChek) and culture. British Co-operative Clinical Group national survey on diagnostic issues surrounding genital herpes.
Using the evidence base on genital herpes: optimising the use of diagnostic tests and information provision. Rapid detection of herpes simplex virus in clinical specimens by centrifugation and immunoperoxidase staining.
Herpes simplex virus detection by macroscopic reading after overnight incubation and immunoperoxidase staining. Polymerase chain reaction for diagnosis of genital herpes in a genitourinary medicine clinic.
Increasing proportion of herpes simplex virus type 1 as a cause of genital herpes infection in college students. Neither ECDC nor any person acting on behalf of ECDC is responsible for the use that might be made of the information in this journal. Some of these diseases can also be picked up in other ways – like through infected needles or unsanitary towels, while some children may inherit them from their mothers. It is accepted that the term STD refers to illnesses that are primarily transmitted through intercourse – for example, meningitis, although possibly transmissible this way, is not considered an STD for the simple reason that this happens in a very small number of cases. While some diseases are more easily transmissible than others, most of them are contagious enough to make it highly likely to get infected in the case of having unprotected sex with an infected person.
However, illnesses like HIV and HPV are just as likely to be transmissible, whether or not the infection has evolved.
However, since skin contact and exchange of other body fluids (like saliva) is quite likely through intercourse (not to mention the occasional condom break cases), the condom is still not a fool proof method.
One can avoid contracting an STD if one pays special attention to the people they get involved with. As is in the case of many other illnesses, STDs have a higher curing chance if caught early. Some clinics even offer low-cost or free testing, based on income.  And if the thought of visiting an STD Test Clinic is scary and potentially embarrassing, there are also STD home test kits available for purchase. It is estimated that 340 million new cases of chlamydia, syphilis, gonorrhea and trichomoniasis occured in 1999 (1 in 20 people in the world was newly infected with one of these diseases), with a considerable proportion of those happening in the African countries and Southeast Asia. The sad part is that, in most cases, prevention and early diagnosis of STDs through STD testing are easy processes and not at all expensive, but they do not occur due to ignorance and negligence. A definitive diagnosis usually can be made on physical examination of the eyelid and a careful evaluation of symptoms and exposures. Cellulitis may be suspected in patients with a red, swollen eyelid, although dermatitis is a more common cause.
In the United States, it affects 10 to 20 percent of children and 1 to 3 percent of adults,28 with eyelid involvement in approximately 15 percent of cases.29ETIOLOGYThe etiology of atopic dermatitis is thought to involve a combination of complex genetic, environmental, and immunologic interactions. It may be classified according to anatomic location: anterior blepharitis affects the base of the eyelashes, whereas posterior blepharitis involves the meibomian gland orifices.
Although these conditions are less common causes of eyelid edema than contact dermatitis and atopic dermatitis, immediate recognition and treatment are critical to prevent vision loss and other serious complications, such as meningitis and cavernous sinus thrombosis.An understanding of the anatomy of the eyelid is important in distinguishing preseptal from orbital cellulitis. This condition may present with swollen eyelids similar to cellulitis; however, it most often occurs bilaterally and concurrently with swelling of other distensible regions of the body, particularly other facial structures and the extremities.
Herpes virus is a DNA virus and 7 viruses of Herpes viridae family have been isolated from humans: HSV1, HSV2, Varicella zoster, Epstein Barr virus (EBV), Cytomegalo virus (CMV), Human herpes virus 6 and 7.
The patients with classic HSE manifest with fever, behavioural abnormality, personality change, focal seizure and aphasia.
If the PCR is negative and patients come in the second week, CSF lgM antibody against HSV is also diagnostic.
In neonatal and immune-compromised HSE patients, double the adult dose of acyclovir is given for 21 days. The most important predictors of outcome are delayed treatment, depth of coma and extremes of age. The World Health Organization (WHO) has estimated a prevalence of herpes simplex virus type 2 (HSV-2) infection of 29 million cases in men and 12.3 million cases in women in eastern Europe and central Asia in 2003 [1]. In contrast, the lesions of infections caused by HSV-2 are usually located below the waist and are usually acquired as a result of sexual contact with infected persons later in life.
The main clinical symptoms, manifestations and complications of genital herpes infections are summarized in Table 2. HSV is the most common cause of sexually acquired genital ulceration, however, the role of causative agents of other STIs, such as Treponema pallidum and Haemophilus ducreyi should not be forgotten. They are a consensus document of the Eastern European Sexual and Reproductive Health (EE SRH) Network [11,12] and comprise one element of a series of guidelines aimed at optimising, standardising and providing guidance on quality assurance of laboratory testing for reproductive tract infections [13-16]. The disadvantages of DIF are that it is time consuming, labour intensive and, compared to NAATs, has a suboptimal sensitivity. Delayed transport of samples to the laboratory and lack of refrigeration during transportation substantially affect the outcome of the testing [31].
Commonly used cells include primary human fibroblasts and cell lines such as MRC-5, Vero cells, baby hamster kidney and rabbit kidney cells [35,36]. Furthermore, compared with traditional PCR, real-time PCR allows detection and typing of HSV in a single reaction tube, is faster (takes approximately two hours to perform), allows simplified conditions of performance and lowers the risk of cross-contamination [37]. These act as indicators of sensitivity, specificity and reproducibility, which are independent of the test systems used. However, directly after infection there is a ‘window’ in which testing for antibodies will give a negative result. However, the minimum requirements for the validation of a new or modified test have also been published [45]. Although the benefits of the serological assays (such as type-specific EISAs) include the possibility of automation and therefore simultaneous processing of a large number of samples at relatively low cost, they have a number of disadvantages that considerably limit their use in the diagnosis of genital herpes.


If NAATs are not available, antigen detection, namely DIF or EIA, could be employed, if high performance of those tests can be assured.
In: International statistical classification of diseases and related health problems, 10th revision, version for 2007. Part 2: culture, non-culture methods, determination of antibiotic resistance, and quality assurance. MSSVD Special Interest Group on Genital Herpes and the British Co-operative Clinical Group.
It is generally assumed that an STD is an illness that may be transmissible in ways other than sexually, but in most cases it is likely that it was contracted through sexual contact. Although in most cases penetrative sex is the most contagious option, diseases can also be transmitted through oral sex; sometimes direct skin contact is sufficient to get an STD.
Unfortunately, since there is no procedure that is capable of detecting all possible STDs, one needs to either test for all of them regularly or pay special attention to all possible symptoms, to know what to test for. Do make sure to use a reputable provider.  You can call one of our STD counselors for more information on STD testing.
The differential diagnosis of eyelid edema is extensive, but knowledge of the key features of several potential causes can assist physicians in diagnosing this condition (Table 1).
Blepharitis is often associated with other disorders such as rosacea, seborrheic dermatitis, and keratoconjunctivitis sicca.35ETIOLOGYThe exact etiology of blepharitis is unknown. The orbital septum is a sheet of connective tissue that extends from the orbital bones to the margins of the upper and lower eyelids37; it acts as a barrier to infection deep in the orbital structures38 (Figure 4). In immune-competent adults, 90% of HSE is due to HSV1 and the remaining 10% are due to HSV2. After the availability of PCR, milder patients with HSE have been recognized with focal or diffuse encephalitis without severe alteration in sensorium and they recover well. MRI finding of frontotemporal involvement is suggestive of HSE in a patient with acute febrile encephalopathy (Fig 1). The international classification of diseases caused by herpes virus (anogenital) [2] is presented in Table 1.
Unfortunately, the differentiation of HSV-1 from HSV-2 based on anatomical site of infection is not absolute, since genital herpes may frequently be caused by HSV-1 as a result of oro-genital sexual practices and vice versa. This episode resolves spontaneously, but recurrences may occur as a result of reactivation of the infection that has become latent but persists in the cervical ganglia. Both oral and genital herpes are manifested by acute recurrences followed by varying periods of latency, when the virus remains in a non-multiplying episomal form in the nuclei of the neurons in the ganglia. They are primarily intended for professionals testing specimens from patients at sexual healthcare clinics but may also be helpful for community-based screening programmes.
The characteristic cytopathic effect of HSV in tissue culture generally appears within 24–72 hours, but may take up to five days. Use of NAATs for diagnosis of HSV also allows less strict sample transportation conditions, compared with those required for diagnosis by culture. Serodiagnosis is useful for documenting newly acquired infections and for diagnosis in persons who present without lesions or with atypical lesions.
It is not always the case that an infected person displays symptoms, but in most of the cases an infected person does spread the infection. Orbital cellulitis is a severe infection presenting with proptosis and ophthalmoplegia; it requires hospitalization and intravenous antibiotics to prevent vision loss. Anterior blepharitis is often attributed to staphylococcal infection or seborrhea, whereas posterior blepharitis generally results from meibomian gland dysfunction.35DIAGNOSISPatients with blepharitis will have erythematous and mildly edematous eyelid margins. Infection of the tissues superficial to the orbital septum is called preseptal cellulitis, whereas infection deep in the orbital septum is termed orbital cellulitis.38 Distinguishing between the conditions is important in determining appropriate treatment. It typically is unilateral and presents with tenderness, erythema, and localized swelling of the lid margin.2,38An internal hordeolum is a staphylococcal infection of a meibomian gland. Similarly, if an individual has not been exposed to HSV-1 in childhood, he or she may develop severe genital lesions following sexual exposure to HSV-2 later in life.
Classically, each episode or recurrence is characterised by a patch of redness at the site of the recurrence, followed by a localised papular then vesicular rash.
Testing for HSV type-specific antibodies can also be used to diagnose HSV-2 infection in asymptomatic individuals [31,40], and other persons with undiagnosed HSV-2 infection. Unfortunately, serological tests alone cannot inform the aetiology of a presenting genital lesion with any degree of certainty. Type-specific serology should be used for detecting asymptomatic individuals, testing pregnant women at risk of acquiring HSV infection close to delivery, men who have sex with men, and people who are HIV positive. Except where otherwise stated, all manuscripts published after 1 January 2016 will be published under the Creative Commons Attribution (CC BY) licence.
Less serious conditions, such as contact dermatitis, atopic dermatitis, and blepharitis, are more common causes of eyelid erythema and edema. Inciting or exacerbating factors include aeroallergens, chemicals, foods, and emotional stress. Soft, oily, yellow scaling or, rarely, brittle scaling around the lashes distinguishes blepharitis from other causes of eyelid inflammation. HSV1 encephalitis has a bimodal distribution- one-third cases occur before 20 years and half the cases after 50 years of age.
However, because HSV-2 is almost always associated with genital disease, whereas HSV-1 is associated with both oro-pharyngeal and genital disease, there is often considerable stigma associated with HSV-2 infection. As with HSV-1 infections, primary HSV-2 infections resolve spontaneously but recurrences are likely to occur as a result of reactivation of latent infection that has been established in the sacral ganglia. The vesicles contain a clear fluid that contains many thousands of infectious viral particles. Non-infectious causes of genital ulceration, such as inflammatory bowel disease (Crohn disease), mucosal ulcerations associated with Behcet syndrome or fixed drug eruption, may also be confused with genital herpes [9]. You are free to share and adapt the material, but you must give appropriate credit, provide a link to the licence, and indicate if changes were made. These less serious conditions can often be managed with topical corticosteroids and proper eyelid hygiene. Patients may have itching, irritation, and burning.2,36 Culture of the eyelid margins may be indicated for patients with recurrent anterior blepharitis and for those unresponsive to therapy. Acquisition of HSV-1 usually results in lesions of the oro-pharynx and around the mouth and on the lips and chin. These vesicles burst, forming shallow ulcers or erosions that eventually crust and heal spontaneously without leaving scars. The types of persons who are recommended to be tested for genital herpes infections are listed in Table 3. Up to 50% of first-episode cases of genital herpes are caused by HSV-1 [41], but recurrences and subclinical viral shedding are much less frequent for genital HSV-1 infection than genital HSV-2 infection [42,43]. It is recommended that any non-validated diagnostic tests should be validated against a recommended, approved gold standard test.
They are differentiated on the basis of such clinical clues as time course, presence or absence of irritative symptoms, scaling, and other skin findings. Biopsy to rule out carcinoma may be needed in particularly recalcitrant cases.35TREATMENTEyelid hygiene is the mainstay of treatment.
These episodes usually last less than 10 days, but may be prolonged as a result of secondary bacterial infection or immunosuppression. Warm compresses are recommended, followed by gentle massage to express meibomian secretions. Such therapies include clindamycin (Cleocin), trimethoprimsulfamethoxazole (Bactrim, Septra), doxycycline (Vibramycin), and minocycline (Minocin).
Sexual transmission of HSV most often produces infection of the genital mucosa, genital skin (penile and labial) and the perigenital region.
In most cases of genital herpes (80–90%) the disease progresses subclinically, but may become symptomatic at any time [5,6]. Virus from genital secretions can also infect other areas, including the eyes and oro-pharynx and rectal mucosa [3,4]. The incubation period of both HSV-1 and HSV-2 is usually from two to 10 days (up to four weeks). Benign, self-limited eyelid nodules such as hordeola and chalazia often respond to warm compresses, whereas malignancies require surgical excision. For patients with staphylococcal blepharitis, a topical antibiotic applied at bedtime for a week or more may speed resolution.



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