Varicella zoster and herpes simplex virus pneumonias

Varicella zoster (VZV) and herpes simplex (HSV) viruses commonly cause self-limited infection of the skin and mucous membranes. However, certain groups of subjects, including neonates, cancer patients, organ and bone marrow transplant recipients and those with congenital or acquired deficiencies of cell mediated immunity, are at increased risk for dissemination of either virus to the lungs and/or other viscera. The highest risk for VZV pneumonitis is in bone marrow transplant recipients, 44%, and in children with acute leukemia, 32%. The mortality from this complication of VZV infection in the preantiviral era was at least 25%. Except for neonates, dissemination and mortality rates for HSV infections are less than for VZV infections in the high risk groups. Cell-mediated immunity has a major role in both recovery from primary infection and modulation of latent infection, but antiherpes antibodies also have an important role in moderating the extent and severity of infection. Both viruses cause a patchy nodular pneumonia with scattered necrotic and hemorrhagic foci. Physical examination is often misleading and rapid progression of pneumonia can occur within hours. Intravenous acyclovir, administered early in the course of HSV and VZV infection at dosages of 250 mg/m2 and 500 mg/m2 every eight hours, respectively, has nearly eliminated the risk of severe symptomatic pneumonitis. Treatment of established pneumonitis with acyclovir at these doses has also reduced the mortality of herpesvirus pneumonias.     

Varicella zoster and herpes simplex virus infections.

There are six herpes viruses, three of which, the varicella-zoster virus and the herpes simplex viruses types 1 and 2, are of particular concern to patients and staff in critical care units. These viruses, especially in their reactivated states, may present atypically in critically ill and immune-suppressed patients, and, by the time the diagnosis is made, exposures of other patients and clinicians may have occurred. Pregnancy and immunosuppressed states can result in severe, even life-threatening varicella-zoster virus infections in susceptible adults. Similarly, nosocomial herpes simplex virus infections can have serious consequences for exposed patients and staff. An additional problem after herpes simplex virus infection is the potential of lifelong and possibly frequent recurrences. In this article, the manifestations, modes of transmission, and treatment will be discussed. Special emphasis will be placed on describing the types of patients who are at high risk of presenting with varicella-zoster virus or herpes simplex virus infection so that physicians and nurses can use appropriate preventive measures to avert nosocomial infections in patients and staff.     

Varicella vaccination in Japan, South Korea, and Europe

The most extensive use of varicella vaccine has been in the United States and Canada, where it is universally recommended. However, a number of other countries now have recommendations for use of the vaccine, which has been expanding in Europe and Latin America. In this article, we review information concerning varicella vaccination in Japan, where the vaccine was first developed, and in South Korea and parts of Europe. Despite the worldwide availability of an efficient vaccine, varicella vaccination policy is highly variable from country to country. The recent development of a tetravalent vaccine against measles, mumps, rubella, and varicella could modify this variability in the future. It is evident that efforts to control varicella will spread gradually to all continents.     

Varicella zoster virus DNA exists as two isomers.

Fragments of varicella zoster virus DNA produced by EcoRI endonuclease cleavage were cloned in vector pACYC 184 and those produced by HindIII cleavage were cloned in pBR322. Restriction enzyme cleavage maps established by double digestion and blot hybridization showed that varicella zoster virus DNA has a Mr of 80 +/- 3 x 10(6) and exists as a population of two isomers.     

Varicella zoster virus meningoencephalitis after allogeneic hematopoietic stem cell transplantation

Although the reactivation of varicella zoster virus (VZV) is a common complication after allogeneic hematopoietic stem cell transplantation (HSCT), VZV meningoencephalitis is a rare life‐threatening infectious disease after HSCT. We describe here a patient who developed VZV meningoencephalitis 2 years after human leukocyte antigen‐matched unrelated HSCT for acute myeloblastic leukemia. She developed chronic graft‐versus‐host disease, and cyclosporine (CSA) was continued until 17 months after HSCT. Low‐dose acyclovir (ACV) at 200 mg/day was administered to prevent the reactivation of VZV from day ?7 to the termination of CSA. At 22 months, she suddenly developed fever, loss of consciousness, and seizure, with generalized skin rash. A high level of VZV DNA was detected in her cerebrospinal fluid (CSF). She was diagnosed to have VZV meningoencephalitis. Intravenous ACV at 30 mg/kg/day was given for 2 months. Although loss of consciousness was quickly resolved, some neurologic symptoms persisted. She did not have any known risk factors for VZV reactivation. Therefore, we should keep in mind that any HSCT recipient may develop VZV meningoencephalitis, and examination of CSF for VZV infection with an empiric administration of ACV may be recommended for HSCT recipients with central nervous system symptoms, even in the absence of skin manifestations.     

Varicella zoster virus DNA at inoculation sites and in saliva after Zostavax immunization

Analysis of 36 individuals over age 60 years who were immunized with Zostavax revealed varicella zoster virus (VZV) DNA in swabs of skin inoculation sites obtained immediately after immunization in 18 (50%) of 36 subjects (copy number per nanogram of total DNA, 28 to 2.1 × 10(6)) and in saliva collected over 28 days in 21 (58%) of 36 subjects (copy number, 20 to 248). Genotypic analysis of DNA extracted from 9 random saliva samples identified vaccine virus in all instances. In some immunized individuals over age 60, vaccine virus DNA is shed in saliva up to 4 weeks.     

Varicella zoster infection and pulmonary complications

A 34-year-old immunocompetent man with varicella zoster (VZ) infection developed deep vein thrombosis and pulmonary embolism after suffering severe pneumonitis. He recovered after treatment with acyclovir, high-dose steroids, and ventilatory support. The endothelial damage could be a direct link between VZ pneumonitis and pulmonary emboli.     

Varicella zoster virus infection associated with high-dose chemotherapy and autologous stem-cell rescue

A retrospective evaluation of 215 consecutive recipients of high-dose chemotherapy (HDC) and autologous stem cell rescue (ASCR) was conducted to ascertain the incidence, temporal course, and outcome of varicella zoster virus (VZV) infection. Herpes zoster was identified in 40 individuals at a median of 69 days following ASCR. Six of these cases occurred at a median of 33 days prior to ASCR but following the initiation of high doses of stem cell mobilization chemotherapy. Twenty-five percent of patients demonstrated cutaneous or systemic dissemination and 32.5% required medical intervention for post-herpetic neuralgia. All except two individuals received antiviral chemotherapy. One patient with active VZV infection died of multiorgan failure 39 days after ASCR. Multivariate analysis of risk factors disclosed the significance of prophylactic acyclovir use in Herpes simplex virus seropositive individuals in reducing the risk of VZV infection. Moreover, the use of busulfan, thiotepa and carboplatin as the conditioning chemotherapy regimen was associated with an increased risk of subsequent VZV infection. The incidence of VZV reactivation after HDC and ASCR is similar to that observed following bone marrow transplantation but has an earlier onset. This may be related to an earlier induction of immunosuppression by stem cell mobilization chemotherapy administered prior to ASCR. We demonstrated a marked reduction in the proliferative and synthetic capacities of peripheral blood mononuclear cells obtained prior to and following stem cell mobilizing chemotherapy. Moreover, greater than 80% of VZV infections occurred within 6 months following ASCR and late cases were seldom observed compared to allogeneic and autologous bone marrow transplantation. The role of antiviral chemoprophylaxis during the period of maximum immunocompromise needs to be studied further in the HDC-ASCR setting.     

Varicella zoster virus meningitis complicating sodium stibogluconate treatment for cutaneous leishmaniasis

Sodium stibogluconate (Pentostam(R); GlaxoSmithKline) is a pentavalent antimonial compound used in the treatment of leishmaniasis, which has an association with reactivation of varicella zoster virus (VZV). We report the first known case of an immunocompetent adult who developed VZV aseptic meningitis and dermatomal herpes zoster during treatment with sodium stibogluconate.     

Varicella zoster virus deoxythymidine kinase is present in serum before the onset of varicella

A sensitive enzyme assay with 125I-iododeoxyuridine as substrate and cytidine triphosphate as phosphate donor was used for the direct detection of varicella zoster virus (VZV) deoxythymidine kinase (TK) in human serum. Sera sampled during the incubation period of varicella from 2 patients, a 42-year-old man and his 11-year-old son, have been analysed for TK activity. A simultaneous increase in cellular and VZV TK activity, starting 5 to 3 days before the onset of clinical varicella, was observed.     

Varicella zoster virus immunity in multinational health care workers of a Saudi Arabian hospital

INTRODUCTION: The health care worker (HCW) is vulnerable to hospital-acquired varicella zoster virus (VZV) infection, and thereafter may transmit infection to coworkers and patients who are susceptible and hospitalized. Interventions to prevent varicella transmission in HCW groups of uncertain immunity prove labor intensive, costly, and disruptive. Therefore, documentation of total varicella immunity in HCWs is desirable. SETTING: The National Guard King Abdulaziz Medical City is a 600-bed tertiary care center in Riyadh, Saudi Arabia with a multinational staff. MATERIAL AND METHOD: A program to assess the VZV status of HCWs was initiated in 1999. The survey was confined to HCWs having direct patient contact. Questions elucidated previous history of varicella (chicken pox) infection, antibody testing against varicella, and varicella vaccination. HCWs with a negative or unknown history were subsequently tested for varicella antibodies (IgG). RESULTS: Seventy-six percent (2,047) of the HCWs responded to the questionnaire. Of these, 562 (28%) were physicians, 761 (37%) were nurses, 438 (21%) were medical technicians, and 286 (14%) were involved in clerical work. A total of 802 (39%) were from the Middle East including Saudi Arabia, 633 (31%) were from the Far East, 361 (18%) were from the West and from temperate areas, 138 (7%) were from South Africa, and 113 (5%) were from other nationalities. A previous history of VZV infection was reported by 1303 (64%); 262 (13%) had a history of positive test for varicella antibody, and only 44 (2%) had a history of varicella vaccination. Of the 744 (36%) HCWs who had a negative or unknown history of VZV infection, 217 (29%) underwent antibody testing. Of these, 181 (83%) proved to be immune (IgG > or = 1.10), and 36 (17%) nonimmune (IgG < 1.2). The latter group have completed varicella immunization. Staff from the West (81%), Far East (78%), and South Africa (59%) reported more histories of VZV infection compared with the employees of Middle Eastern origin (46%) (P <.001) and disclosed a history of positive antibodies in 13%, 18%, 17%, and 8%, respectively (P <.001). In relation to occupation, nurses reported history of varicella infection (75%) and a history of positive varicella antibodies (16%) more than physicians (54% and 8%, respectively) (P <.05). Conversely, serologic immunity to VZV infection proved consistent among the different nationalities and among the 4 occupational groups. CONCLUSION: Total varicella immunity of a multinational workforce can be realized through screening of HCWs and vaccination of susceptible individuals. It is preferred above repeated interventions after varicella exposure for its simplicity, cost-effectiveness, and efficiency. Knowledge of VZV infection varies between different nationalities and cannot be used as a true predictor of immunity. There is no difference in the immunity by antibody testing of staff recruited from temperate and tropical climates. Total varicella immunity should, therefore, be achieved through screening of all HCWs and vaccination of those susceptible.     

Varicella zoster meningoencephalitis following treatment for dermatomal zoster in an alloBMT patient

Herpes zoster infections are frequently observed after allogeneic bone marrow transplantation (alloBMT). In the majority of cases, the infection is restricted to specific dermatomes and responds to oral acyclovir, without visceral dissemination. We report the case of a 40-year-old male who developed dermatomal herpetic infection 8 months post alloBMT. The herpetic rash responded well to treatment with high-dose oral acyclovir. However, within a week of cessation of therapy, the patient re-presented with dermatomal zoster and meningoencephalitis. Although the cutaneous lesions resolved with intravenous acyclovir, clinical features of meningoencephalitis persisted, along with evidence of varicella zoster virus (VZV) DNA in cerebrospinal fluid (CSF). A satisfactory response to treatment was observed only after the addition of intravenous foscarnet to acyclovir. Based on our experience with this patient, we suggest that in a subset of alloBMT recipients, late dermatomal herpes zoster infections may respond only partially to treatment with standard oral acyclovir. The use of oral acyclovir preparations with higher bioavailability (valacyclovir) or intravenous acyclovir early on may prevent the considerable morbidity associated with disseminated zoster infection. Bone Marrow Transplantation (2000) 26, 795-796.