A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

BACKGROUND: The incidence and severity of herpes zoster and postherpetic neuralgia increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). We tested the hypothesis that vaccination against VZV would decrease the incidence, severity, or both of herpes zoster and postherpetic neuralgia among older adults. METHODS: We enrolled 38,546 adults 60 years of age or older in a randomized, double-blind, placebo-controlled trial of an investigational live attenuated Oka/Merck VZV vaccine ("zoster vaccine"). Herpes zoster was diagnosed according to clinical and laboratory criteria. The pain and discomfort associated with herpes zoster were measured repeatedly for six months. The primary end point was the burden of illness due to herpes zoster, a measure affected by the incidence, severity, and duration of the associated pain and discomfort. The secondary end point was the incidence of postherpetic neuralgia. RESULTS: More than 95 percent of the subjects continued in the study to its completion, with a median of 3.12 years of surveillance for herpes zoster. A total of 957 confirmed cases of herpes zoster (315 among vaccine recipients and 642 among placebo recipients) and 107 cases of postherpetic neuralgia (27 among vaccine recipients and 80 among placebo recipients) were included in the efficacy analysis. The use of the zoster vaccine reduced the burden of illness due to herpes zoster by 61.1 percent (P<0.001), reduced the incidence of postherpetic neuralgia by 66.5 percent (P<0.001), and reduced the incidence of herpes zoster by 51.3 percent (P<0.001). Reactions at the injection site were more frequent among vaccine recipients but were generally mild. CONCLUSIONS: The zoster vaccine markedly reduced morbidity from herpes zoster and postherpetic neuralgia among older adults.

Malignant external otitis: a severe form of otitis in diabetic patients.

Two cases of malignant external otitis are presented and the literature is reviewed. The disease seems to occur exclusively in elderly diabetic patients. Diagnosis is mostly a clinical one, and requires a high index of suspicion. The characteristic clinical manifestations are pain and severe tenderness of the tissues around the ear and mastoid, persistent drainage and the presence of granulation tissue at the junction of the osseus and cartilagenous portions of the external ear. Roentgenographic findings are not helpful in the early stages. The pathogenesis of this disease depends on the presence of clefts in the cartilage forming the floor of the external auditory canal at its junction with the osseus portion through which infection can spread from the external ear to the deep soft tissues. Serious and often fatal complications may ensue. The most common and earliest symptom to appear if facial nerve palsy. Pseudomonas aeruginosa has been isolated uniformly, in pure or mixed cultures. This entity, therefore, should be borne in mind whenever an elderly diabetic patient presents with external otitis not amenable to the usual methods of therapy. Ps. aeruginosa should be strongly suspected, and its isolation should prompt vigorous systemic treatment with gentamicin and carbenicillin before extensive necrosis of cartilage and bone takes place. Any delay in diagnosis and management will lead to a serious and often fatal complications.

Normal T cell subsets in homosexual men living in a community without endemic AIDS.

The cause of the abnormal T lymphocyte subsets reported in healthy homosexual men is not known. Frequent sexually transmitted infections including human T cell lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) are possible causes. To determine if the T lymphocyte subsets were abnormal in this population in an area without endemic acquired immune deficiency syndrome (AIDS), T lymphocyte subsets of 52 homosexual men in Rochester, New York, were enumerated, and evidence of infections known to cause these abnormalities was sought. Unlike the findings in previous reports, relative numbers of T helper and T suppressor cells and helper/suppressor T cell ratios were normal. Prevalence of cytomegalovirus infection (86 percent) was similar to that found in analogous populations, but only 9 percent had seropositive results for HTLV-III/LAV. Men with serologic evidence of nonprimary cytomegalovirus disease had lower helper/suppressor T cell ratios (1.5 +/- 0.2 versus 2.2 +/- 0.2; p less than 0.01). Hence, despite frequent infections with cytomegalovirus and other sexually transmitted pathogens, T cell subsets are normal in homosexual men in an area without endemic AIDS. Therefore, HTLV-III/LAV is primarily responsible for the T cell abnormalities observed elsewhere.

Lymphocytic choriomeningitis in university hospital personnel. Clinical features.

Clinical manifestations of lymphocytic choriomeningitis (LCM) virus infection in 15 patients are described. These patients were University Hospital personnel who had had contact with hamsters, subsequently shown to harbor the virus. Fever with striking myalgias, headache and rigors were the most common symptoms. Only 2 of the 15 patients had clinically overt and documented aseptic meningitis. Leuikpenia was observed in 10 of 11 patients and thrombocytopenia in 8 of 8 patients tested. A biphasic illness was seen in eight patients. In a patient who has been exposed to laboratory animals, particularly to hamsters, a nonspecific influenza-like febrile illness accompanied by leukopenia and thrombocytopenia may represent LCM virus infection.

Cytomegalovirus infection blocks the beneficial effect of pretransplant blood transfusion on renal allograft survival.

Two factors which have gained attention as possible contributors to success of renal allografts are freedom from infection with cytomegalovirus (CMV) after transplant and administration of multiple blood transfusions pretransplant. In order to determine the interrelationship of these two variables, we analyzed 55 recipients of well matched (at least two antigens) cadaveric kidneys. In this study, absence of CMV infection and receipt of multiple transfusions both provided favorable outcomes. When patients were grouped by both factors, those who were free of infection and received multiple transfusions did significantly better than any other combination. Infection with CMV decreased the frequency of allograft survival in multiply transfused patients to a point intermediate between the above group and those who had not been multiply transfused. Since CMV infection can be predicted by measurements made pretransplant, and since up to one-quarter of CMV infection which develops post-transplant is transmitted with the allograft, administration of multiple transfusion to all patients and the use of donors who are free of latent CMV infection for CMV antibody-negative potential recipients should increase allograft success. For those potential recipients who already have latent CMV infection, further study will be necessary to determine what stimuli can be given pretransplant to prevent the interference with the beneficial effect of multiple transfusion.

Multicenter seroepidemiologic study of the impact of cytomegalovirus infection on renal transplantation.

The effects of cytomegalovirus (CMV) infection on patient and allograft survival were determined in 1245 renal transplant recipients from 46 transplant centers. When an antilymphocyte preparation was administered to cadaveric allograft recipients, those at risk for primary CMV had a worse outcome than similar patients treated with prednisone and azathioprine (53.1% alive at 6 months with a functioning allograft vs. 70.8%, P = .05) or patients at risk for reactivation CMV (53.1% vs. 71.1%, P = .035). Patients at risk for reactivation CMV had a better outcome if they received an antilymphocyte preparation (71.1% vs. 60.8%, P less than .01). The type of immunosuppression had no effect on patients without CMV. Living-related donor transplantation was not significantly influenced by CMV or type of immunosuppression. We conclude that CMV infection is strongly influenced by the form of immunosuppression employed, and that both are important determinants of the outcome of cadaveric renal transplantation.

Acquired immunodeficiency syndrome-related visceral leishmaniasis presenting in a pleural effusion.

Visceral leishmaniasis is increasingly reported in immunocompromised patients, including patients with AIDS. We report a case of visceral leishmaniasis in an AIDS patient who presented with pulmonary symptoms and bilateral pleural effusions. Histologic evaluation of pleural fluid and bone marrow revealed histiocytes with intracellular Leishmania amastigotes. Visceral leishmaniasis should be considered in AIDS patients with a significant travel history who present with unexplained pulmonary symptoms.

Viral respiratory infections in the institutionalized elderly: clinical and epidemiologic findings.

OBJECTIVE: To prospectively evaluate the incidence and impact of viral respiratory infection in the institutionalized elderly during a winter season. DESIGN: Prospective descriptive study, without intervention. METHOD: Patients with respiratory illnesses were evaluated by a directed history and physical examination. Nasopharyngeal secretions for viral culture were obtained, and acute and convalescent serum samples were obtained for analysis. Serologic evidence of infection with respiratory syncytial virus (RSV) and parainfluenza were determined by enzyme immunoassay (EIA), and influenza by hemagglutination-inhibition assay and EIA. SETTING: A 591-bed nursing home. PARTICIPANTS: Residents with signs or symptoms of acute respiratory illness (nasal congestion, pharyngitis, cough, wheezing, or respiratory difficulty) were eligible for study. RESULTS: A viral etiology was documented in 62 out of 149 illnesses (42%). RSV was the most common virus associated with illness; it was documented in 27% of respiratory illnesses, followed by rhinovirus (9%), parainfluenza (6%), and influenza (1%). RSV was associated with significantly more severe disease when compared with rhinovirus. Clustering of specific viral infections occurred, suggesting nosocomial transmission. CONCLUSIONS: Viruses are an important cause of acute respiratory infections in the institutionalized elderly during the winter months.

Studies with live attenuated influenza vaccines.

Inhibitor-resistant and temperature-sensitive live attenuated influenza virus vaccines were administered to normal volunteers and elderly and chronically ill persons to assess safety, antigenicity, and transmissibility. Recombinants of both types of vaccine were made using currently prevalent influenza virus strains (A/Hong Kong/68, A/England/42/72, A/Scotland/74, A/Victoria/75) over a five-year period to keep the vaccine relevant with regard to antigenic drift. The results indicate that both vaccine types are safe, antigenic and non-transmissible and that for both types of vaccines, recombinants can be made to new antigenic drifts. The inhibitor-resistant vaccine replicates to lower titers in the nasopharynx than the temperature-sensitive virus, and this is considered an advantage, whereas the genetic defect of the temperature-sensitive virus is better defined than that of the inhibitor-resistant vaccine.

Communitywide laboratory-based influenza surveillance focused on older persons, 1989-1992.

We collected surveillance data as part of the Medicare Influenza Vaccine Demonstration to describe communitywide epidemiology of influenza, focusing on the elderly. Laboratory-based surveillance was established in medical practices, hospitals, and nursing homes in a two-county demonstration in upstate New York. Time course and intensity of epidemic influenza were compared between counties, between influenza A and B epidemics, and among several levels of surveillance involving elderly persons as well as children during the years 1989-1992. The counties experienced parallel epidemics during each of the three demonstration years. Influenza A/H3N2, predominant in 1989-1990 and 1991-1992, was equally intense among young and old, accounted for 11%-28% of acute cardiopulmonary hospitalizations of older persons, and caused focal outbreaks in 30%-40% of nursing homes in the respective epidemics. Influenza B, predominant in 1990-1991, showed modest impact among the elderly as compared with children. Influenza A/H1N1 occurred among children each year but was virtually absent among the elderly. Systematic surveillance during the "influenza season" consistently confirms widespread infection among older patients, both in the community and in institutions. However, much febrile respiratory illness in this age group during periods of epidemic influenza is culture-negative for influenza virus and thus may be caused by other respiratory pathogens.

Varicella pneumonitis: clinical presentation and experience with acyclovir treatment in immunocompetent adults.

OBJECTIVE: Cases of varicella pneumonitis were reviewed to examine the effects of acyclovir therapy on outcome. METHODS: A retrospective chart review was done of all admissions of adults to two hospitals, between 1985 and 1995, because of complications of chickenpox. RESULTS: Fifteen patients were hospitalized for varicella pneumonitis during this period. No patient had a history of chickenpox as a child; all had a recent history (within 2-4 weeks prior to admission) of exposure to chickenpox in their family or neighborhood and developed respiratory symptoms 1 to 4 days after the appearance of the rash. Twelve patients (80%) had a history of cigarette smoking, and seven patients had a platelet count below the normal range. All patients were treated with intravenous acyclovir within 24 hours of admission, and all but one survived and were discharged from the hospital without comorbid conditions. The one mortality was attributed to bacterial superinfection. CONCLUSIONS: Acyclovir treatment may be of benefit for varicella pneumonitis, but no controlled trial has been performed to definitively answer this question.

Atypical invasive external otitis from Aspergillus.

We report a rare case of invasive external otitis caused by aspergillosis in an elderly nondiabetic patient. Amphotericin B therapy was curative. Atypical features of the presentation delayed diagnosis. Early use of tissue biopsy and culture to guide prompt initiation of therapy is recommended. The clinical spectrum and microbiology of invasive aspergillosis are also reviewed.

Antiviral agents in respiratory infections.

Viral respiratory illnesses are among the most common afflictions in the United States. Until recently, few agents were available to control these infections. Now, there are specific and nonspecific agents either to prevent or treat viral respiratory infections. For example, a better understanding of the pathogenesis of the common cold provided new insights into therapeutic intervention for that entity. In other instances (eg, influenza), the antiviral agent is so specific that there is a need for diagnostic information to guide therapy. Epidemiological clues, clinical symptoms, and some newer laboratory methods all contribute to the clinician's understanding of the cause of an individual respiratory illness and guide the choice of therapy. In other circumstances, information is being gradually developed that points toward the availability of a broad-spectrum antiviral drug with activity against at least five of the important respiratory viruses; its major limitation is that a cumbersome and expensive means of delivery to the patient is required. For such a drug to gain widespread use, a more practical method of delivery is necessary.

Amantadine and rimantadine for the prevention of influenza A.

Influenza is a leading cause of morbidity and mortality in the United States, particularly among persons with cardiac and/or pulmonary disease and those over age 65. Vaccine is effective but not completely protective. Prophylaxis with one of the antivirals, amantadine or rimantadine, has proven efficacy against influenza A virus infections. It should be considered for high-risk patients both in the community and in health care facilities where these subjects are concentrated. Prophylaxis also has potential benefit in the home when an index case of acute influenza has been identified. The dose of drug that is most appropriate is under study. Based on observations made in young patients, it is hoped that rimantadine will be better tolerated by the elderly than has been the case with amantadine. Assessment of efficacy in outbreaks caused by viruses of different antigenic make up and elevation of the significance of drug resistance will be important in judging the true value of prophylaxis of influenza with either of these antivirals.

Vaccines in the prevention of viral pneumonia.

Vaccines to control respiratory virus infections have been limited to inactivated whole virus or split virus product of influenza. Over the last few years, advances in the understanding of immunity to and importance of these infections has led to the development of newer, more immunogenic inactivated influenza vaccines and to the exploration of live attenuated influenza vaccines. In parallel, both inactivated and live attenuated vaccines against respiratory syncytial virus and parainfluenza virus have been undergoing evaluation. More effective or new vaccines could reduce morbidity, reduce the frequency of hospitalization, and decrease the death rate. Since viral respiratory disease would be decreased in frequency, vaccines could reduce the use of antibiotics, and by so doing, preserve the usefulness of our currently available antibiotics.

Approaches to improved influenza vaccination.

Inactivated influenza vaccine (Ivac) has had an important impact on reducing attack rates of influenza and reducing the severity of illness amongst the vaccinees who still acquire infection. Ivac is most efficacious amongst young, otherwise healthy subjects and least effective against elderly at high risk. This is in part because Ivac does not appear to significantly reduce infection rates and in part because response rate and final antibody titer are lower in the elderly. Therefore Ivac does not eliminate disease in the elderly who are prone to complications when any virus replication occurs. Simultaneous administration of intra-nasal live attenuated influenza vaccine (Livac) and Ivac reduces the infection rate and thus illness rate amongst high-risk elderly. Presumably this is because of the ability of Livac to stimulate secretory antibody which neutralizes virus at the mucosal surface. Other approaches are examining the benefit of baculovirus recombinant vaccine or adjuvanted Ivac to determine if the higher serum antibody these vaccines produce compared to Ivac, will diffuse onto the mucosal surfaces and in a similar fashion, neutralize virus at that site.