Trends in mortality due to invasive mycotic diseases in the United States, 1980-1997.

To determine national trends in mortality due to invasive mycoses, we analyzed National Center for Health Statistics multiple-cause-of-death record tapes for the years 1980 through 1997, with use of their specific codes in the International Classification of Diseases, Ninth Revision (ICD-9 codes 112.4-118 and 136.3). In the United States, of deaths in which an infectious disease was the underlying cause, those due to mycoses increased from the tenth most common in 1980 to the seventh most common in 1997. From 1980 through 1997, the annual number of deaths in which an invasive mycosis was listed on the death certificate (multiple-cause [MC] mortality) increased from 1557 to 6534. In addition, rates of MC mortality for the different mycoses varied markedly according to human immunodeficiency virus (HIV) status but were consistently higher among males, blacks, and persons > or =65 years of age. These data highlight the public health importance of mycotic diseases and emphasize the need for continuing surveillance.

Multicenter case-control study of risk factors for histoplasmosis in human immunodeficiency virus-infected persons.

We conducted a multicenter case-control study to identify risk factors for histoplasmosis among persons with acquired immunodeficiency syndrome (AIDS) and to evaluate predictors of a poor outcome (defined as death or admission to the intensive care unit). Patients with histoplasmosis were each matched by age, sex, and CD4 lymphocyte count to 3 controls. From 1996 through 1999, 92 case patients and 252 controls were enrolled. Of the case patients, 81 (89%) were men, 50 (55%) were black, 78 (85%) had a CD4 lymphocyte count of <100 cells/microL, 80 (87%) were hospitalized, and 11 (12%) died. Multivariable analysis found that receipt of antiretroviral therapy and of triazole drugs were independently associated with a decreased risk of histoplasmosis. Chronic medical conditions and a history of infections with herpes simplex virus were associated with poor outcome. Triazoles should be considered for chemoprophylaxis for persons with AIDS, especially those who take part in high-risk activities that involve frequent exposure to soil, who have CD4 lymphocyte counts of <100 cells/microL, and who live in areas where histoplasmosis is endemic.

Evaluation of effectiveness of the 23-valent pneumococcal capsular polysaccharide vaccine for HIV-infected patients.

BACKGROUND: We conducted a retrospective case-control study to evaluate effectiveness of pneumococcal vaccine against invasive disease among adults with human immunodeficiency virus (HIV) infection in San Francisco, Calif, and Atlanta, Ga. METHODS: Case patients were 18- to 55-year-old subjects with HIV infection who were admitted to selected hospitals in Atlanta or San Francisco from February 1992 to April 1995 from whom Streptococcus pneumoniae was isolated from a normally sterile site. Controls were HIV-infected patients of similar age matched to cases by hospital of admission and CD4 lymphocyte count (<0.20, 0.20-0.499, >/=0.50 x 10(9)/L [<200, 200-499, >/=500 cells/mm(3)]) or clinical stage of acquired immunodeficiency syndrome. Case and control subjects were restricted to persons known to have HIV infection before hospital admission. Analysis used matched univariate and conditional logistic regression. RESULTS: One hundred seventy-six case patients and 327 controls were enrolled. By univariate analysis, persons with pneumococcal disease were more likely to be black, be current smokers, and have close contact with children. Adjusted for these factors and CD4 cell count, pneumococcal vaccine effectiveness was 49% (95% confidence interval [CI], 12%-70%). Adjusting for all variables and key interaction terms, vaccine effectiveness among whites was 76% (95% CI, 35%-91%), whereas effectiveness among blacks was 24% (95% CI, -50% to 61%). Among controls, vaccination was significantly less common among blacks (29% vs 45%; P<.005). CONCLUSIONS: Pneumococcal vaccine demonstrated protection against invasive pneumococcal infections among white but not black HIV-infected adults. Failure to demonstrate effectiveness among blacks may be due to limited power because of low use of the vaccine in this population, immunization at more advanced stages of immunosuppression, or unmeasured factors. These data support current recommendations for use of pneumococcal vaccine in HIV-infected persons and highlight a clear need for strategies to improve vaccine-induced protection.

Risk factors for morbidity and mortality after colectomy for colon cancer.

PURPOSE: Comorbid conditions affect the risk of adverse outcomes after surgery, but the magnitude of risk has not previously been quantified using multivariate statistical methods and prospectively collected data. Identifying factors that predict results of surgical procedures would be valuable in assessing the quality of surgical care. This study was performed to define risk factors that predict adverse events after colectomy for cancer in Department of Veterans Affairs Medical Centers. METHODS: The National Veterans Affairs Surgical Quality Improvement Program contains prospectively collected and extensively validated data on more than 415,000 surgical operations. All patients undergoing colectomy for colon cancer from 1991 to 1995 who were registered in the National Veterans Affairs Surgical Quality Improvement Program database were selected for study. Independent variables examined included 68 preoperative and 12 intraoperative clinical risk factors; dependent variables were 21 specific adverse outcomes. Stepwise logistic regression analysis was used to construct models predicting the 30-day mortality rate and 30-day morbidity rates for each of the ten most frequent complications. RESULTS: A total of 5,853 patients were identified; 4,711 (80 percent) underwent resection and primary anastomosis. One or more complications were observed in 1,639 of 5,853 (28 percent) patients. Prolonged ileus (439/5,853; 7.5 percent), pneumonia (364/5,853; 6.2 percent), failure to wean from the ventilator (334/5,853; 5.7 percent), and urinary tract infection (292/5,853; 5 percent) were the most frequent complications. The 30-day mortality rate was 5.7 percent (335/5,853). For most complications, 30-day in-hospital mortality rates were significantly higher for patients with a complication than for those without. Thirty-day mortality rates exceeded 50 percent if postoperative coma, cardiac arrest, a pre-existing vascular graft prosthesis that failed after colectomy, renal failure, pulmonary embolism, or progressive renal insufficiency occurred. Preoperative factors that predicted a high risk of 30-day mortality included ascites, serum sodium >145 mg/dl, "do not resuscitate" status before surgery, American Society of Anesthesiologists classes III and IV OR V, and low serum albumin. CONCLUSIONS: Mortality rates after colectomy in Veterans Affairs hospitals are comparable with those reported in other large studies. Ascites, hypernatremia, do not resuscitate status before surgery, and American Society of Anesthesiologists classes III and IV OR V were strongly predictive of perioperative death. Clinical trials to decrease the complication rate after colectomy for colon cancer should focus on these risk factors.

Outcome after proctectomy for rectal cancer in Department of Veterans Affairs Hospitals: a report from the National Surgical Quality Improvement Program.

OBJECTIVE: To define risk factors that predict adverse outcomes after proctectomy for cancer in Department of Veterans Affairs Medical Centers. SUMMARY BACKGROUND DATA: Accurate presurgical assessment of the risk of perioperative complications and death is important in planning surgical therapy. METHODS: The National VA Surgical Quality Improvement Program contains prospectively collected and extensively validated data on >287,000 patients. All patients undergoing proctectomy for rectal cancer from 1991 to 1995 who were registered in this data base were selected for study. Independent variables examined included 68 presurgical and 12 intraoperative clinical risk factors; dependent variables were 21 specific adverse outcomes. Stepwise logistic regression analysis was used to construct models predicting 30-day morbidity rates for each of the 10 most common complications and the 30-day mortality rate. RESULTS: Five hundred ninety-one patients were identified; 467 (79%) underwent abdominoperineal resection and 124 (21%) were treated with sphincter-saving procedures. Thirty percent of patients had one or more complications after proctectomy. Prolonged ileus, urinary tract infection, pneumonia, and deep wound infection were the most frequently reported complications. The 30-day mortality rate was 3.2% (19 deaths). For most complications, 30-day mortality rates were significantly higher for patients with complications than for those without. Thirty-day mortality rates for several complications exceeded 50%: cardiac arrest requiring cardiopulmonary resuscitation, deep venous thrombosis or thrombophlebitis, coma lasting >24 hours, acute renal failure, cerebrovascular accident, and pulmonary embolism. Four presurgical factors predicted a high risk of 30-day mortality in the logistic regression analysis: elevated blood urea nitrogen level, impaired sensorium, low serum albumin concentration, and partial thromboplastin time < or =25 seconds. CONCLUSIONS: Mortality rates after proctectomy in VA hospitals are comparable to those reported in other large series. Most postsurgical complications are associated with an increased 30-day mortality rate. Elevated presurgical blood urea nitrogen level, impaired sensorium, low serum albumin concentration, and partial thromboplastin time < or =25 seconds predict a high risk of 30-day mortality.

Detection of human immunodeficiency virus core protein in plasma by enzyme immunoassay. Association of antigenemia with symptomatic disease and T-helper cell depletion.

A sensitive enzyme immunoassay was developed for detecting human immunodeficiency virus (HIV) core antigen. Assay sensitivity was 3.67 pmol/L of purified HIV core protein, and 1 or 100 in-vitro infectious units/mL of HIV in purified virus preparations or cell culture supernatants, respectively. Enzyme immunoassay sensitivity exceeded that of reverse transcriptase assay by 1000-fold. Core antigen was detected in whole plasma from 41% of symptomatic subjects and 13% of asymptomatic subjects seropositive for HIV. After plasma fractionation, antigenemia was found in 60% of symptomatic subjects and in 33% of asymptomatic subjects seropositive for HIV. Fifty-seven percent of samples from which HIV could be isolated in lymphocyte culture had detectable quantities of core antigen in plasma. However, at least 87% of samples with measurable antigen in plasma had HIV isolated from lymphocyte cultures. Antigenemia was associated with reduced T-cell number and symptomatic disease, and may be a useful marker for disease progression.

Inactivation of human T-cell lymphotropic virus, type III by heat, chemicals, and irradiation.

Infectivity of human T-cell lymphotropic virus, Type III (HTLV-III) was inactivated by heat more rapidly if in liquid medium than if lyophilized and more rapidly at 60 degrees than 56 degrees C. When HTLV-III was added to factor VIII suspension, then lyophilized and heated at 60 degrees C for 2 hours or longer there was elimination of 1 X 10(6) in vitro infectious units (IVIU) of virus. Much of the viral inactivation appeared to result from lyophilization. The application of water-saturated chloroform to the lyophilized material containing virus also resulted in elimination of infectivity. HTLV-III was efficiently inactivated by formalin, beta-propiolactone, ethyl ether, detergent, and ultraviolet light plus psoralen. The results are reassuring regarding the potential safety of various biological products.

Development of subtype-specific and heterosubtypic antibodies to the influenza A virus hemagglutinin after primary infection in children.

Children undergoing primary infection with an H1N1 or H3N2 influenza A virus developed subtype-specific hemagglutination inhibition antibodies and enzyme-linked immunosorbent assay antibodies to purified hemagglutinin (HA) of the infecting virus subtype. They also developed lower titered ELISA antibodies to the noninfecting H1 or H3 HA and to H8 (an avian strain) HA. Thus, after primary infection with an influenza A virus, children develop enzyme-linked immunosorbent assay, but not hemagglutination inhibition, antibodies reactive with heterosubtypic HAs. These heterosubtypic antibodies could influence the response to infection with other wild-type or attenuated vaccine strains of influenza A virus.

Characterization of nematocyst proteins from the sea anemones Aiptasia pallida and Pachycerianthus torreyi (Cnidaria: Anthozoa).

Nematocysts from the anemones Aiptasia pallida and Pachycerianthus torreyi were investigated. SDS-polyacrylamide electrophoresis of solubilized Aiptasia nematocysts revealed one major protein band (mol. wt 31,800) and several minor components. Coelectrophoresed whole venom contained numerous protein components, of which a major one appeared to be identical to the major nematocyst protein. Nematocyst capsules and everted threads from both species contained levels of glycine and proline-hydroxyproline characteristic of vertebrate collagens. Cysteine was present in significant amounts. Aiptasia whole venom contained high levels of glutamic acid and/or glutamine (71%) with no detectable cysteine or proline-hydroxyproline. The 31,800-dalton venom protein possessed only glycine (80%) and glutamyl and/or glutaminyl (20%) residues.

Gradient optimization principles in reversed-phase high-performance liquid chromatography and the separation of influenza virus components.

Reversed-phase high-performance liquid chromatography is used to separate the major proteins of A/Bangkok/1/79 X 73 influenza virus. The purity of the isolated proteins, their yield and reactivity with monoclonal antibodies are discussed. The virus, in turn, is used as a probe to examine some theoretical gradient principles relating resolution, retention time and gradient time. Empirical compliance with these principles is generally shown.

Secretory immunological response after intranasal inactivated influenza A virus vaccinations: evidence for immunoglobulin A memory.

An intranasal, inactivated trivalent influenza A vaccine containing 7 micrograms of A/Bangkok/1/79 (H3N2) hemagglutinin was administered to 20 children aged 1 to 6 years to assess the local and systemic immune responses to antigen delivered to the respiratory tract. Six children without prior influenza virus infection exhibited no local immune response and manifested only a minimal systemic response to the intranasal vaccine. In contrast, five individuals who were previously infected with a live attenuated influenza A H3N2 virus vaccine, although having no residual secretory antibody at the time of challenge, promptly developed a local antibody response to intranasal, inactivated antigen. Therefore, the live influenza A virus vaccine had induced memory in the local immunoglobulin A (IgA) immune system. The third group of nine children had previously been infected with wild-type H3N2 influenza virus. A majority of these children had residual local and systemic antibody at the time of challenge but they demonstrated some boosting of local IgA antibody with administration of intranasal inactivated vaccine. The competence of the secretory IgA immune system in young children in mounting primary and secondary responses to influenza antigens has important implications for approaches to prevention of influenzal illness.

Secretory and systemic immunological response in children infected with live attenuated influenza A virus vaccines.

An enzyme-linked immunosorbent assay was used to measure isotype-specific antibody to purified hemagglutinin (HA) of influenza A virus, using serum and nasal-wash specimens from young children undergoing primary infection with live cold-adapted influenza A/Alaska/77 (H3N2) or A/Hong Kong/77 (H1N1) candidate vaccine virus. The serum antibody response followed the pattern expected for a primary viral infection. Each of 17 vaccinated children had a serum immunoglobulin G (IgG) HA antibody response, 16 had an IgM antibody response, and 13 had an IgA antibody response. Nasal-wash HA antibody was detected in the IgA, IgM, and IgG isotypes. Of the 17 vaccinated children, 14 had an IgA response, 13 had an IgM response, and 9 had an IgG response. Most of the IgA and IgM HA antibody was actively secreted locally, whereas only some of the IgG HA antibody could be shown to be actively secreted into the respiratory tract. There was a good correlation between the level of nasal-wash antibodies measured by the HA-specific IgA enzyme-linked immunosorbent assay and by a plaque neutralization assay. These data indicate that intranasal vaccination of susceptible children with live, attenuated, cold-adapted influenza A viruses efficiently stimulates both systemic and local antibody responses.

Mitogenicity of influenza hemagglutinin glycoproteins and influenza viruses bearing H2-hemagglutinin.

The hemagglutinin glycoprotein is responsible for the mitogenic effect of influenza A viruses of the H2N2 subtype. This was indicated by the ability of viruses bearing the H2-hemagglutinin glycoprotein, regardless of its associated neuraminidase, to induce lymphocyte proliferation in normal spleen cell suspensions and by the ability of antisera with specificity for the H2-hemagglutinin to block this response. Moreover, purified hemagglutinin from representative viruses from the H0N1, H1N1, H2N2, H3N2, and influenza B subtypes were also shown to be mitogenic.

Hemagglutinin-specific enzyme-linked immunosorbent assay for antibodies to influenza A and B viruses.

An enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies present in human serum or nasal washes directed against influenza A or B hemagglutinin glycoproteins. The assay was modified to measure the immunoglobulin isotype specificity of the anti-hemagglutinin response in serum and nasal secretions. In the postinfection sera anti-hemagglutinin of the immunoglobulin G isotype was predominant, whereas in nasal secretions the antibody was predominantly immunoglobulin A. The antibody response detected by the ELISA manifested hemagglutinin subgroup specificity. In addition, there was a good correlation between the ELISA antibody titer and the hemagglutination-inhibition or neutralizing antibody titer. The ELISA was more sensitive than the hemagglutination-inhibition assay, and the range of antibody titers measurable by ELISA in human serum was from less than 1:20 for children who had never experienced influenza infection to 1:400,000 for adults convalescing from a secondary infection. With more sensitive tests to detect antibody to the influenza hemagglutinin it should be possible to determine the relative contribution of local and systemic immunity to resistance to influenza virus infection.