SEROPREVALENCE OF HERPES SIMPLEX VIRUS IN DERMATOLOGY PATIENTS

The group of herpesvirus are of DNA viruses. Their replication is intranuclear and produces typical intranuclear inclusions. Virus persists throughout the person's life as a latent infection in the cells for which the strain is specific. Under certain conditions, especially immune suppression, the virus may become reactivated and produce an acute infection ¹.Herpes simplex is caused by herpesvirus hominis (HSV). It is one of the commonest human infections worldwide. There are two major antigenic types: type 1, which is classically associated with facial infections; and type 2, which is typically genital, although there is considerable overlap in disease manifestations ¹.After primary infection, both type 1 and type 2 HSV persists in sensory nerve ganglia. The virus may travel peripherally along the nerve fibre, and, if it replicates in the skin or mucous membrane, it may cause recurrent disease. The virus can be shed in saliva and genital secretions from asymptomatic individuals, especially in the months following the first episode of disease. Examples of exogenous inoculation are lesions of the hand in health care workers, facial lesions contracted during contact sports, and infection of a breastfeeding mother's nipples from the infected mouth of her baby.Following primary infection, cell-mediated and humoral immune responses takes place. They do not fully protect against reinfection or recurrent disease. The incidence and severity of both primary and recurrent herpetic infections may be increased especially in immune suppressed patients.Immunological abnormalities, in addition to possible local cutaneous factors, may explain the increased incidence in atopic eczema of recurrent herpes simplex and the evolution in some individuals of erythema multiforme. Herpetic recurrences are associated with temporary depression of cell-mediated immunity in otherwise healthy individuals. In several regions of the world the prevalence of HSV-1 infection has been found to be higher than that of HSV-2 infection ². Seroconversion and rising antibodies titres distinguish primary from recurrent infection. Antibodies remain indefinitely in the blood and serological tests are used to detect them. Although viral culture is an important diagnostic tool and western blot analysis is an epidemiological golden standard, they are available only in few centres.  Type – specific ELISA is a very effective method in detecting HSV antibodies ³. Employing this method we have studied the seroprevalence of herpes simplex virus type 1 and type 2 in blood samples from dermatology patients. We believe that this study is the first of its kind in Saudi Arabia will contribute to the understanding of herpes simplex virus serology in Saudi Arabia (SA)^4-6.The aim of this study is to assess the seroprevalence of HSV skin infections (HSV-1 and HSV-2 antibodies) among patients attending a dermatology clinic at King Fahd Hospital of the University (KFHU).

MATERIAL & METHODS

The study was conducted in the dermatology clinic at King Fahd Hospital of the University, Al-Khobar, Saudi Arabia, from November 2006 to May 2007. One hundred fifty consecutive samples of blood drawn from dermatology patients for various laboratory workup were tested for HSV IgG and IgM antibodies. The method employed was type-specific ELISA (Gull, USA). The results of the method were interpreted according to the recommendations of the manufacturer.Clinical assessment (history and physical examination) and interview-based questionnaire was conducted for all patients attending the dermatology clinics. All patients attending with skin disease requiring blood workup were assessed for type-specific HSV antibodies. 

RESULTS

The age of the patients ranged from 2 years to 63 years (mean 31 years). Males were 63 and females 87. The clinical presentation varied and included: eczema, vitiligo, herpetic infections, urticaria, atopic dermatitis, acne, tinea capitis, tinea pedis, pityriasis rosea, hair fall, chicken pox, hirsutism, psoriasis, alopecia and erythema multiforme, etc.133 (88.7%) patients’ samples had detectable levels of HSV-1 IgG antibodies whereas 4 (2.6%) samples had detectable level of HSV-2 IgG antibodies. Two samples (1.3%) had detectable levels of HSV-1 IgM antibodies and none of the samples had detectable level of HSV-2 IgM. There was correlation between HSV-1 IgM positivity (N=2) and a clinical diagnosis of herpetic infections.

Discussion:

Seroepidemiological surveys have yielded valuable information on the prevalence and incidence of HSV infection in general and in selected populations ^7-13. Many of these studies identify risk factors associated with HSV infection, while others allow assessment of the impact of prevention strategies.The prevalence of HSV skin infections in Skaraborg, Sweden, was assessed among approximately 7,500 indi­viduals over 7 years of age and was found to be about 1% ¹. In another Swedish study performed in dermatol­ogy clinics, 2% of men and 1.5% of women attending clinics in Gothenburg over a 6-year period had evidence of herpetic skin infections ⁷. In addition to individu­als with atopic disease, patients with skin abrasions or bums appear particularly susceptible to HSV-I or HSV-2 infections, and some may develop disseminated infection ³. Disseminated HSV infections were also reported among wrestlers, and this is referred to as herpes gladito­rium ⁷. Other skin disorders associated with exten­sive cutaneous lesions include Darier's disease and Sezary's syndrome ⁸. As would be predicted, localized recurrences followed by a second episode of dissemination were observed. HSV infections of either type were found to trigger erythema multiforme. The association of HSV DNA in skin lesions of erythema multiforme is as high as 80% ¹.The seroprevalence of HSV-1 antibody in France was 68% ¹. This is considerably lower than the values obtained in our study (88.7% for HSV-1). HSV-1 seropositivity is known to increase with age. The seroprevalence of HSV-2 in the French study in the same population was 17.3% ¹  whereas in our study it was 2.6% in our study. Since HSV-2 is mainly sexually transmitted, the difference in the HSV-2 seropositivity between the two studies could be explained by the differences in the sexual habits between the two communities. Data on sexually transmitted infections (STIs) in Saudi Arabia (SA) and other Islamic countries are very limited. Recently, STIs in SA was found to be low when compared to other countries such as the United States ¹⁴. For example, in 1999, the average incidence of gonorrhea per 100,000 populations in the United States was 131.4, whereas, in SA, it was 4.9. It is estimated that 1 million cases of herpes are reported every year in the United States. The data on STIs may well be underrepresented because of the possibility of underreporting. United Nations and the World Health Organization data on HIV prevalence in different countries showed that the prevalence of HIV infection in Islamic countries is strikingly low compared to other countries ¹⁴. The seropositivity for HSV-1 IgG antibodies in our study (88.7%) confirms the findings of previous investigators ^4-6,15.The estimated seropositivity of HSV-2 IgG antibodies in our study (2.6%) is significantly less than the HSV-2 IgG antibodies reported by Ghazi et al (27.1%). This could well be due to regional variations within Saudi Arabia.Detectable IgM antibodies in HSV infection usually reflect current or recent infection. In fact, all IgM-positive patients gave symptoms and signs suggestive of HSV infections. None of the other skin diseases in our study group was associated with IgM positivity. Presence of detectable HSV IgG antibodies usually indicates previous exposure.

Conclusion

The seroprevalence of HSV-1 in our dermatology patients is high. HSV-1 and HSV-2 can infect all age group and may result in significant morbidity. Assessment of HSV infection will help in the proper management of HSV infection as well as for epidemiological purposes.

ACKNOWLEDGEMENT

The financial support from the Deanship of Scientific Research at King Faisal University (grant No. 7072) is gratefully acknowledged.

REFERENCES

1. Whitley RJ: Herpes Simplex Viruses. In Knipe DM, Howley PM, Griffin DE et al eds. Fields Virology. 4^th ed. Vol 2. New York: Lippincott, 2001: 2461-2509.
2. Wald A, Corey L, Cone R, Hobson A, Davis G, Zeh J. Frequent genital her­pes simplex virus 2 shedding in immunocompetent women: effect of acyclovir treatment, J Clin Invest 1997; 99:1092-7.
3. Goodyear HM, Wilson P Cropper L, et al: Rapid diag­nosis of cutaneous herpes simplex infections using spe­cific monoclonal antibodies, Clin Exp Dermatol 1994; 19:294-7.
4. Ashley RL, Wu L, Pickering JW, Tu MC, Schnorenberg L. Premarket evalu­ation of a commercial glycoprotein G-based enzyme immunoassay for herpes simplex virus type-specific an­tibodies, JClin Microbiol 1998; 36:294-5.
5. KurtzJB: Specific IgG and IgM antibody responses in herpes-simplex virus infections, Med Microbiol 1994; 7:333-41.
6. Koutsky LA, Stevens CE, Holmes KK, et al: Under-diagnosis of genital herpes by current clinical and viral-isolation procedures, N Engl J Med 1992; 326:1533-9.
7. Kulhanjian JA, Soroush V, Au DS, et al: Identification of women at unsuspected risk of primary infection with   herpes simplex virus type 2 during pregnancy, N Engl J Med 1992; 326:916-20.
8. Frenkel LM, Garratty EM, Shen JP, Wheeler N, Clark O, Bryson YJ. Clinical reacti­vation of herpes simplex virus type 2 infection in se­ropositive pregnant women with no history of genital herpes, Ann Intern Med 1993; 118:414-8.
9. Brown ZA, Selke S, Zeh J, et al: The acquisition of her­pes simplex virus during pregnancy, N Engl J Med 1997; 337:509-15.
10. Brown ZA, Benedetti J, Ashley R, et al: Neonatal her­pes simplex virus infection in relation to asymptomatic maternal infection at the time of labor, N Engl J Med 1991; 324:1247-52.
11. Hossain A.: Herpes simplex virus type 1 (HSV-1) and varicella-zoster virus (VZV) infections in Saudi Arabia, J Trop Pediatr 1989; 35:171-4.
12. Ghazi HO. Seroepidemiological prevalence of IgG antibodies to Herpesviruses in the human population of Makkah. Oxford Res. Forum J 2003; 1:23-6.
13. Alzahrani AJ, Obeid OE, Almulhim AA et al. Analysis of Herpes Simplex 1 and 2 IgG and IgM Antibodies in Pregnant Women and their Neonates. Saudi J Obstet Gynaecol 2005; 5(1):53-59
14. Hossain A, Bakir TF, Siddiqui MA et al. Genital herpes simplex virus infections: laboratory confirmation in diverse patient groups. Int J Gynaecol Obstet 1989; 29:51-6.
15. Tariq A Madani. Sexually transmitted infections in Saudi Arabia. BMC Infect Dis. 2006; 6: 3.