**5. Herpes simplex virus**

Herpes simplex virus type 1 (HSV1) and herpes simplex virus type 2 (HSV2) are members of the Herpesvirus family and is transmitted via close personal contact. Seroprevalence studies indicated that infections are common worldwide and increases with age [2, 69]. More than 90% of adult have acquired HSV infection by their fifth decade of live, though only a minority develop clinically apparent disease at the time of acquisition [70]. After the first contagion, HSV stays in latent condition for a lifetime. HSV1 is acquired predominantly during childhood age, while HSV2 is acquired by sexual contact. A recent study indicated that HSV1 can also cause genital herpes (71). In immunocompetent individuals, symptomatic disease is presented as orolabial or genital herpes [72, 73]. Symptomatic disease may occur as a first episode that heals in 10–21 days, followed by the establishment of latency and the risk of subsequent episodes of reactivation. Cell-mediated immunity plays an important role in host defense and the containment of infection [74]. Individuals with impaired cell-mediated immunity, such as immunosupressed and transplanted patients, are subject to more frequent episodes of reactivation, prolonged duration of symptoms and shedding, increased severity of infection, and a greater potential for dissemination [75]. Solid organ transplant patients have had pretransplant HSV seropositivity rates and age distributions similar to the general population. In the absence of antiviral prophylaxis, seropositive recipients often experience reactivation of latent infection within one or two months after transplantation [76]. Mucocutaneous lesions are the majority of HSV disease in transplant population, mainly with orolabial and anogenital localizations. HSV esophagitis, pneumonia, meningitis, and viremia dissemination either from reactivation or primary infection, may involve the spread to multiple organs such as the liver, adrenal glands, gastrointestinal tract, lungs, skin, and bone marrow [77].

To determine the risk of HSV primary infection or reactivation after immunosupression and transplantation, all patients being considered for these procedures should undergo serologic testing (ELISA anti HSV1 IgG and anti HSV2 IgG) to document prior exposure to the viruses. Patients who are seronegative are at high risk for the development of primary HSV, and seropositive patients are at high risk for developing reactivation. In the presence of character‐ istic mucocutaneous lesions, clinical diagnosis may be considered reliable. Laboratory testing can be used for atypical cases and should be used for suspected disseminated, visceral disease, or central nervous system disease. Viral culture is the definitive method of diagnosis for isolation of the virus from vesicles, urine, stool, nasopharynx, throat, conjunctive, and cerebrospinal fluid. Nucleic acid amplification method of DNA detection (PCR) is increasing utility, and has been shown to be 3 to 4 times more sensitive than viral culture [79]. Direct fluorescent antibody test is another mode of diagnosis of HSV; it offers rapid diagnosis and can also give type-specific diagnoses [75–79].

Acyclovir is the drug of choice for treatment of HSV infections in both immunocompetent and immunocompromized patients. Transplant patients with mucocutaneous lesions may be treated with IV acyclovir (5 mg/kg/dose given every 8 hours) for 7–14 days, oral acyclovir, or one of the alternative oral antiviral agents with better bioavailability (valacyclovir or famcy‐ clovir). Disseminated infections and herpes simplex encephalitis, due to the potentially lifethreatening nature of these infections, should be treated with a high dose IV acyclovir (10 mg/ kg/dose given every 8 hours) for 7–14 days. Recently, in the last few years, some mutated acyclovir resistant strains of HSV have been isolated. These mutants are founded in patients with HIV and those with bone marrow transplantation and preventive treatment with acyclovir. These patients are treated according to a scheme with pencyclovir [76]. Gancyclovi, valgancyclovir, foscarnet or cidofovir are other antiviral agents with activity against herpes‐ viruses, including HSV and CMV co-infections. Acyclovir can also be used for prophylaxis of the infection before immunosuppression and transplantation to prevent reactivation of the latent infection and considerably reduced incidence of disease in the early posttransplant period.

Numerous efforts have been made to develop an HSV vaccine using several different methods including inactivated virus, live attenuated virus, viral subunits and more recently, recombi‐ nant viruses. Many of these attempts shower promising results in their early phase of devel‐ opment [79–80].
