Incidence of herpes zoster in patients with altered immune function.

PURPOSE: To estimate the incidence of herpes zoster (HZ) and rates of post-zoster pain in both the total study population and separately in patients with selected conditions/treatments associated with altered immune function. METHODS: The health administrative claims databases for commercially insured, Medicare, and Medicaid populations, together accounting for approximately 51 million insured individuals, were analyzed between 2005 and 2009 in a retrospective cohort study. Incidence of HZ episodes per 1,000 person-years (PY) was estimated in all study populations as well as within nine potentially immune-altering conditions. Among patients with HZ, the 6-month rate of persistent post-zoster pain was estimated. RESULTS: Analysis of 90.2 million PY at risk revealed that the incidence of HZ in the total study population was 4.82/1,000 PY. The incidence of HZ was highest among patients with bone marrow or stem cell transplant (43.03 %) followed by solid organ transplant, human immunodeficiency virus infection, and systemic lupus erythematosus [95 % confidence interval (CI) 15.19-17.41 %]. HZ incidence rates were higher among persons on immunosuppressants/chemotherapy than among non-users. In the total study population, HZ incidence increased with age (18-49 years: 3.37/1,000 PY; 65+ years: 8.43/1,000 PY; P < 0.01) and female gender (incidence ratio vs. male 1.39, 95 % CI 1.38-1.40 %). The 6-month rate of persistent post-zoster pain was 4.29 % (95 % CI 4.22-4.36 %), which was higher in patients with the selected conditions. CONCLUSIONS: Despite providing a relatively small fraction of overall HZ cases, persons with immune function-altering conditions make a large contribution to the societal healthcare burden because they have a higher risk of developing HZ and persistent post-zoster pain. These risk factors should be considered in HZ prevention efforts.

The tuberculin test. Studies of the dynamics of reactivity to tuberculin and Candida antigen in institutionalized patients.

To determine the importance of the recall phenomenon ("booster effect") in chronically hospitalized patients, we performed three sequential tuberculin and Candida antigen skin tests in patients at two hospitals. Twenty of 162 patients (12.3%) demonstrated a significant reaction on the initial tuberculin test, and 9 additional patients (5.5%) showed a significant reaction (booster response) to a second tuberculin test administered 3 wk later. Five patients (3.1%) demonstrated a significant reaction only when a third tuberculin test was administered 6 wk after the initial test. Only 1 patient (0.6%) with a significant tuberculin reaction on the first 2 tests was nonreactive on the third test. Nineteen patients (11.7%) demonstrated a significant response to Candida antigen on the initial test and a booster effect was noted in 11 (6.2%) and 6 (3.7%) patients, respectively, on subsequent tests. Four patients (2.5%) appeared to lose reactivity to Candida antigen on each of the 2 repeat tests. Only 25% of patients who demonstrated a tuberculin booster response had a significant reaction to the initial Candida skin test. Serial skin tests may be necessary to reliably determine the ability of a chronically hospitalized patient to demonstrate a response to tuberculin.

Epidemiology of tuberculous infection in a chronic care population.

A prospective study of serial tuberculin skin testing was performed on 642 patients from the chronic care wards of a Veterans Administration Hospital. Five hundred eighty-eight patients without a documented history of tuberculosis or a positive tuberculin skin test received an initial 5 TU PPD, and results in 139 were positive (23.6%). Of those initially tuberculin negative, 398 received a second 5 TU PPD 2 to 4 wk later; 45 (11.3%) showed a booster effect. Of the initial 642 patients, 64 had documented negative tuberculin skin tests within the year preceding the survey. Eight (12.5%) of the 64 patients were positive at the initial survey. There were 213 patients with 2 negative tuberculin tests within the first 4 wk of the study who were followed for the year of the study, and 10 converted their tuberculin skin test for a converter rate of 4.7%. The decrease in the converter rate from 12.5 to 4.7% suggests that the initial converter rate was falsely elevated by the booster effect. The high rate of conversion during the year of the study (4.7%) suggests that there may have been inapparent spread of tuberculous infection among patients in this chronic care facility.

Infection of a macrophage-like cell line, P388D1 with reovirus; effects of immune ascitic fluids and monoclonal antibodies on neutralization and on enhancement of viral growth.

We studied the effect of antibody on the growth of reovirus, serotypes 1 and 3, in P388D1, a continuous mouse macrophage-like cell line. Enhanced growth of virus was observed when cells were infected in the presence of nonneutralizing monoclonal antibodies or subneutralizing concentrations of either immune ascitic fluids or neutralizing monoclonal antibodies. Both enhancement of viral growth and neutralization were accompanied by an antibody-mediated increase in binding of radiolabeled virus to P388D1 cells. Although neutralization was seen only with monoclonal antibodies directed toward the sigma-1 surface protein of the virus, enhancement was observed with two monoclonal antibodies directed toward other surface proteins. Trypsin treatment of P388D1 cells abrogated enhanced growth of virus mediated by a mouse IgG2a antibody; preincubation with P388D1 with human IgG1 but not IgG2 myeloma proteins also abrogated enhancement by immune ascitic fluid or monoclonal antibody. These observations are compatible with known properties of P388D1 Fc receptors and support the role of the Fc receptor in antibody-mediated infection.

Transformation by polyoma virus alters expression of a cell mutation affecting cycle traverse.

A temperature-sensitive mutant of hamster BHK 21/13 cells, tsAF8, which at 39 degrees becomes arrested in the G1 (G0) phase of the cell cycle, is phenotypically altered with respect to temperature sensitivity after transformation with polyoma virus. Polyoma transformation does not produce reversion to a non-temperature-sensitive phenotype but causes increased entry into S and increased rate of cell death at the nonpermissive temperature, compared to untransformed tsAF8 cells. The increased frequency of cells synthesizing DNA is not accompanied by an increased frequency of mitosis, since most of the polyoma-transformed tsAF8 cells that synthesize DNA at the nonpermissive temperature do not divide. At the permissive temperature, polyoma-transformed tsAF8 cells, unlike tsAF8, also lose viability when exposed to other methods of arresting cells in G1. The most likely explanation for this phenomenon is that polyoma virus transformation interferes with the cellular response to this mutation as well as to other conditions that cause cell cycle arrest in G1.

Multiplication of polyoma virus in mouse-hamster somatic hybrids: a hybrid cell line which produces viral particles containing predominantly host deoxyribonucleic acid.

The multiplication of polyoma virus in a mouse-hamster (3T3 x BHK) somatic hybrid line (10A), which, although permissive for viral multiplication, produces very low amounts of virus, has been studied. In this cell line, the efficiency of productive infection is high, but the yield of infectious virus is on the order of 0.5% of that of 3T3 cells. The amount of viral deoxyribonucleic acid (DNA) synthesized by these cells upon infection is about 5% of that of 3T3 cells. An examination of the virus produced in hybrid 10A revealed that it was only one-tenth as infectious as the virus grown in 3T3. Although the viral DNA synthesized in the infected 10A cells is normal, the DNA extracted from purified virus grown in 10A consists of approximately 10% of normal, supercoiled polyoma DNA molecules and of approximately 90% linear DNA molecules with a sedimentation coefficient of 14 to 16S. These DNA molecules appear to be of cellular origin but contain a limited amount of viral DNA sequences. The host DNA-containing particles are not infectious but appear to possess some biological activity; they give rise to a weak complementation effect, and part of them are able to induce T-antigen synthesis. In addition, the host DNA present in these particles is predominantly that which has been synthesized after infection. The correlation between the block in viral DNA synthesis in this cell line and the abnormal encapsidation of host DNA is discussed.