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P C Hopewell

Publications and source records attributed to P C Hopewell.

At least 19 recordsLinked to original sources

Incidence of tuberculosis in the United States among HIV-infected persons. The Pulmonary Complications of HIV Infection Study Group.

BACKGROUND: The resurgence of tuberculosis in the United States is largely linked to the human immunodeficiency virus (HIV) epidemic. Despite this link, the epidemiology of tuberculosis and preventive strategies in patients infected with HIV are not completely understood. OBJECTIVES: To determine the incidence and predictors of tuberculosis in HIV-infected persons. DESIGN: Prospective, multicenter cohort study. SETTING: Community-based cohort of persons with and without HIV infection at centers in the eastern, midwestern, and western United States. PARTICIPANTS: 1130 HIV-seropositive patients without AIDS who were followed for a median of 53 months (814 homosexual men, 261 injection drug users, and 55 women who had acquired HIV through heterosexual contact). MEASUREMENTS: Delayed hypersensitivity response to purified protein derivative (PPD) tuberculin and mumps antigen, CD4 T-lymphocyte counts, and frequency of tuberculosis. RESULTS: 31 HIV-seropositive patients developed tuberculosis (0.7 cases per 100 person-years [95% CI, 0.5 to 1.0]). The most important demographic risk factor was location (adjusted risk ratio for eastern compared with midwestern and western United States, 4.1 [CI, 2.0 to 8.4]). Tuberculosis occurred more frequently in persons with CD4 counts of less than 200 cells/mm3 (1.2 cases per 100 person-years [CI, 0.7 to 1.9]) than in those with higher counts (0.5 cases per 100 person-years [CI, 0.3 to 0.8]). The rate of tuberculosis was highest among tuberculin converters (5.4 cases per 100 person-years [CI, 1.1 to 15.7]), lower among patients who were PPD positive at first testing (4.5 cases per 100 person-years [CI, 1.6 to 9.7]), and lowest among patients who remained PPD negative (0.4 cases per 100 person-years [CI, 0.2 to 0.7]). Tuberculosis was not reported among persons who had PPD reactions of 1 to 4 mm. Compared with that of patients who tested positive for mumps, the risk for tuberculosis of those who tested negative was increased about sevenfold if they were PPD positive (P < 0.03) and fourfold if they were PPD negative (P < 0.02). CONCLUSIONS: Incidence of tuberculosis was higher in the eastern United States, in patients with CD4 counts of less than 200 cells/mm3, and in PPD-positive patients. Analysis of tuberculin reaction size supports the current interpretive criteria of the Centers for Disease Control and Prevention. Nonreactivity to mumps antigen indicated increased risk for tuberculosis independent of PPD response.

AIDS-Related Opportunistic Infections

Predictors of Pneumocystis carinii pneumonia in HIV-infected persons. Pulmonary Complications of HIV Infection Study Group.

The Pulmonary Complications of HIV Infection Study is a prospective, multicenter, observational study evaluating pulmonary disease among HIV-infected persons. For approximately 52 mo, 1,182 HIV-infected subjects were followed. All participants were evaluated for pulmonary disease on a predetermined schedule. There were 145 episodes of Pneumocystis carinii pneumonia (PCP). Low CD4 count correlated with risk of PCP (p < 0.0001); 79% had CD4 counts less than 100/microl and 95% had CD4 counts less than 200/microl. Subtle changes in diffusing capacity for carbon monoxide (DLCO) were associated with PCP. Univariate analysis identified recurrent undiagnosed fevers, night sweats, oropharyngeal thrush, and unintentional weight loss to be associated with risk among persons with CD4 counts above 200/microl. Subjects in whom CD4 counts declined to below 200/microl and who were not receiving preventive therapy were nine times more likely to develop PCP within 6 mo compared with subjects who received such therapy. A strong trend toward differences between the sexes was detected. Black subjects had less than one third the risk of developing PCP as did white subjects (p < 0.0001). There was no significant difference in risk by HIV transmission category, study site, frequency of follow-up, age, education, smoking history, or use of antiretroviral therapy. Multivariable analysis revealed low CD4 lymphocyte count (p < 0.0001), use of prophylaxis (p < 0.0001), racial differences (p < 0.0001), and declining DLCO (p = 0.015) to influence risk. Constitutional signs and symptoms indicate increased risk for PCP among HIV-infected persons with CD4 counts above 200/microl.

AIDS-Related Opportunistic Infections

Intensive care of patients with HIV infection: utilization, critical illnesses, and outcomes. Pulmonary Complications of HIV Infection Study Group.

To examine intensive care unit (ICU) admission rates and diagnoses of patients with HIV infection, and to determine the outcomes of different critical illnesses, we analyzed data derived from the 63 patients who were admitted to an ICU from among the 1,130 adults with HIV infection who did not have AIDS at the time of enrollment in a multicenter prospective study. Patients were admitted and treated according to the judgment of their physicians. During 4,298 patient-years of follow-up for the entire cohort, there were 1,320 hospital admissions, of which 68 (5%) included admission to an ICU. Twenty-five (40%) of the patients admitted to the ICU died during that admission. Twenty-four patients (38%) were admitted with a principal diagnosis of lung disease; 11 had Pneumocystis carinii pneumonia (PCP), one of whom was coinfected with Aspergillus fumigatus and Legionella pneumophilia, and six of them (55%) died. Four had bacterial pneumonia, two had pulmonary edema caused by renal failure, and one each had pulmonary tuberculosis, pulmonary Kaposi's sarcoma, pneumothorax, adult respiratory distress syndrome, severe pulmonary fibrosis, cytomegalovirus pneumonitis, and metastatic adenocarcinoma to the lungs. Eleven of these 14 patients (79%) died. Thirty-nine patients had 44 admissions for nonpulmonary diagnoses, including gastrointestinal disorders (14 admissions), cardiovascular disorders (nine), sepsis syndrome (six), neurologic disorders (four), monitoring and ICU nursing care during or after a procedure (four), metabolic disorders (three), trauma (two), drug overdose (one), and unknown reasons (one). Nine (23%) of these patients died. Twenty-eight patients underwent mechanical ventilation, and 16 (57%) died. Seven (25%) had PCP (five died), seven had other primary pulmonary diseases (six died), and 14 were placed on mechanical ventilation for nonpulmonary disorders (five died). Survival did not correlate with CD4 count determined within 6 mo of admission to the ICU. In conclusion, the range of indications for critical care in patients with HIV infection is diverse. PCP accounted for only 16% of the ICU admissions, and mechanical ventilation for PCP and other pulmonary disorders was associated with a high mortality rate. In contrast, mechanical ventilation for nonpulmonary disorders, and admission to the ICU for nonpulmonary diagnoses was associated with a more favorable outcome.

Adult

Respiratory disease trends in the Pulmonary Complications of HIV Infection Study cohort. Pulmonary Complications of HIV Infection Study Group.

We examined trends in the incidence of specific respiratory disorders in a multicenter cohort with progressive human immunodeficiency virus (HIV) disease during a 5-yr period. Individuals with a wide range of HIV disease severity belonging to three transmission categories were evaluated at regular intervals and for episodic respiratory symptoms using standard diagnostic algorithms. Yearly incidence rates of respiratory diagnoses were assessed in the cohort as a whole and according to CD4 count or HIV transmission category. The most frequent respiratory disorders were upper respiratory tract infections, but the incidence of lower respiratory tract infections increased as CD4 counts declined. Specific lower respiratory infections followed distinctive patterns according to study-entry CD4 count and transmission category. Acute bronchitis was the predominant lower respiratory infection of cohort members with entry CD4 counts > or = 200 cells/mm3. In cohort members with entry CD4 counts of 200 to 499 cells/mm3, the incidence of bacterial and Pneumocystis carinii pneumonia each increased an average of 40% per year. In members with entry CD4 counts < 200 cells/mm3, acute bronchitis, bacterial pneumonia, and P. carinii pneumonia occurred at high rates without discernible time trends, despite chemoprophylaxis in more than 80% after Year 1, and the rate of other pulmonary opportunistic infections increased over time. Each year, injecting drug users had a higher incidence of bacterial pneumonia than did homosexual men. The yearly rate of tuberculosis was < 3 episodes/100 person-yr in each entry CD4 and HIV-transmission group. We conclude that the time trends of HIV-associated respiratory disorders are determined by HIV disease stage and influenced by transmission category. Whereas acute bronchitis is prevalent during all stages of HIV infection, incidence rates of bacterial pneumonia and P. carinii pneumonia rise continuously during progression to advanced disease. In advanced disease, the incidence of acute bronchitis, bacterial pneumonia and P. carinii pneumonia is high despite widespread chemoprophylaxis.

AIDS-Related Opportunistic Infections

Nonspecific airway hyperresponsiveness in HIV disease. Pulmonary Complications of HIV Infection Study Group.

OBJECTIVES: HIV disease is frequently complicated by episodic acute bronchitis, suggesting the presence of chronic bronchial inflammation. To further examine this concept, we investigated the possible association of nonspecific airway hyperresponsiveness (AHR) and HIV disease. DESIGN: Methacholine inhalation challenge studies were performed on 66 HIV-seropositive and 8 HIV-seronegative members of the Pulmonary Complications of HIV Infection Study Cohort. AHR was defined as 20% or more decline in FEV1 from the postdiluent value after inhalation of 125 or less cumulative breath units. The prevalence of AHR in HIV-seropositive cohort members was compared with that in matched control subjects who had undergone methacholine challenge testing for two unrelated studies. Demographic, behavioral, and clinical features in HIV cohort members with and without AHR were contrasted. The relationship between AHR and the occurrence of episodic airway disease or symptoms suggestive of airway disease was examined. RESULTS: AHR was not more prevalent in HIV-seropositive cohort members than control subjects (19.3% vs 12.9%; p > 0.1). Within the cohort, AHR was detected more frequently in members with than without a history of asthma (60% vs 16%; p < 0.05). A greater proportion with than without AHR had 1 or more episode of pneumonia within 2 years (46% vs 9%; p < 0.01), 1 or more asthma episode during the study period (39% vs 1.9%; p < 0.001), or wheeze noted during clinic visits (62% vs 17%; p < 0.01). The proportion that experienced acute bronchitis did not differ in the two groups. CONCLUSIONS: This study suggest that HIV-infected persons do not have increased prevalence of nonspecific AHR. In HIV disease, AHR is associated asthma, but not episodic acute bronchitis. Thus, the possibility that airway injury without demonstrable AHR might complicate HIV disease remains.

Adult

The changing epidemiology of acquired drug-resistant tuberculosis in San Francisco, USA.

BACKGROUND: The increasing incidence of tuberculosis caused by drug-resistant Mycobacterium tuberculosis is thought in part to reflect inadequate implementation of standard tuberculosis control measures. However, in San Francisco, USA, which has an effective tuberculosis control programme, we have recently observed an increase in cases of acquired drug-resistance. METHODS: To explore further this observation, we analysed the secular trend of acquired drug-resistance and conducted a population-based case-control study of all reported tuberculosis cases in the city of San Francisco between 1985 and 1994. FINDINGS: We identified 14 patients with tuberculosis caused by fully susceptible M tuberculosis who subsequently developed drug-resistance. Of these acquired drug-resistance cases, two occurred between 1985 and 1989, whereas 12 occurred between 1990 and 1994 (p = 0.028). In the case-control study, AIDS (odds ratio 20.2, 95% CI 1.12-363.6), non-compliance with therapy (19.7, 1.66-234.4), and gastrointestinal symptoms (11.5, 1.23-107.0) were independently associated with acquired drug-resistance. Between 1990 and 1994, one in 16 tuberculosis patients with AIDS and either gastrointestinal symptoms or non-compliance developed acquired drug- resistance. INTERPRETATION: The substantial increase in acquired drug- resistance in San Francisco seems to be a product of the increasing prevalence of HIV/M tuberculosis coinfection. Our data suggest that the interface of the HIV and tuberculosis epidemics fosters acquired drug-resistance, and that traditional tuberculosis control measures may not be sufficient in communities with high rates of HIV infection.

AIDS-Related Opportunistic Infections

Control strategies for tuberculosis epidemics: new models for old problems.

Tuberculosis, although preventable and curable, causes more adult deaths than any other infectious disease. A theoretical framework for designing effective control strategies is developed and used to determine treatment levels for eradication, to assess the effects of noneradicating control, and to examine the global goals of the World Health Organization. The theory is extended to assess how suboptimal control programs contribute to the evolution of drug resistance. A new evaluation criterion is defined and used to suggest how control strategies can be improved. In order to control tuberculosis, treatment failure rates must be lower in developing countries than in developed countries.

Adult

Lack of usefulness of radiographic screening for pulmonary disease in asymptomatic HIV-infected adults. Pulmonary Complications of HIV Infection Study Group.

OBJECTIVE: To determine the use of chest radiographs in the screening of asymptomatic adults infected with the human immunodeficiency virus (HIV). METHODS: A prospective, multicenter study of the pulmonary complications of HIV infection in a community-based cohort of persons with and without HIV infection. The subjects included 1065 HIV-seropositive subjects without the acquired immunodeficiency syndrome at the time of enrollment: 790 homosexual men, 226 injection drug users, and 49 women with heterosexually acquired infection. Frontal and lateral chest radiographs were performed at 3-, 6-, and 12-month intervals, CD4 lymphocyte measurements at 3- and 6-month intervals, tuberculin and mumps skin tests at 12-month intervals, and medical histories and physical examinations at 3- and 6-month intervals. Pulmonary diagnoses that occurred within 2 months following each radiograph were analyzed and correlated with the radiographic results. RESULTS: Evaluable screening chest radiographs (5263) were performed in HIV-seropositive subjects while they were asymptomatic; of these, 5140 (98%) were classified as normal and 123 (2%) as abnormal. A new pulmonary diagnosis was identified within 2 months following a screening radiograph in 55 subjects. Only 11 of these subjects had abnormal radiographs; the sensitivity of the radiograph was 20%. The sensitivity was similarly low at baseline, within each transmission category, and in subjects whose CD4 lymphocyte counts were less than 0.2 x 10(9)/L (200/microL). The types of pulmonary diseases that occurred were similar in the subjects with normal and abnormal screening radiographs. CONCLUSION: Screening chest radiography in asymptomatic HIV-infected adults is unwarranted because the diagnostic yield is low.

AIDS-Related Opportunistic Infections

Mycobacterial complications of HIV infection.

Tuberculosis is the most common opportunistic infection worldwide and is caused by the only readily transmissible pathogen among persons with HIV infection. If treatment is initiated promptly and is supervised appropriately, cure, fortunately, is highly likely. Isoniazid preventive therapy substantially reduces the risk of tuberculosis in persons with HIV infection. Of the nontuberculous mycobacteria, Mycobacterium avium complex (MAC) is the most frequent cause of disease; however, disseminated MAC disease usually is not seen until the CD4+ cell count is less than 50 cells/L. Newer agents, such as the macrolides and rifabutin, form the nucleus of treatment regimens and also are effective in preventing the disease.

AIDS-Related Opportunistic Infections

Overall and cause-specific mortality in a cohort of homo-/bisexual men, injecting drug users, and female partners of HIV-infected men. Pulmonary Complications of Human Immunodeficiency Virus Infection Study Group.

OBJECTIVE: To study the overall and cause-specific HIV-related mortality in a cohort of HIV-seropositive subjects according to transmission category, race/ethnicity, sex and severity of immunosuppression. DESIGN: A cohort of 1129 HIV-seropositive homo-/bisexual men, injecting drug users, and female partners of HIV-infected men were enrolled at six centers in San Francisco, Los Angeles, Chicago, Newark, Detroit and New York between 1 November 1988 and 1 November 1989. Subjects were evaluated every 6 months at least until 31 March 1994. METHODS: The analyses of overall mortality for the subgroups of interest were performed with Kaplan-Meier plots and Cox proportional hazards models. Cause-specific analyses were performed on the primary cause of death using rates per 100 person-years of exposure. RESULTS AND CONCLUSIONS: Baseline severity of immunosuppression is the strongest predictor of mortality. There were no statistically significant differences in overall HIV-related mortality among transmission categories, race/ethnicity groups or sexes. There were differences, however, in cause-specific mortality among the different risk groups.

AIDS-Related Opportunistic Infections

Presentation of AIDS-related pulmonary Kaposi's sarcoma diagnosed by bronchoscopy.

Kaposi's sarcoma (KS) is the most common neoplasm in persons infected with the human immunodeficiency virus (HIV). However, information about the presenting features of pulmonary KS is limited. To describe the clinical, laboratory, and radiographic features of pulmonary KS, medical records and chest radiographs of 168 patients with pulmonary KS diagnosed by bronchoscopy during a 7-yr period were reviewed. All of the patients were HIV-seropositive males, of whom 95% identified homosexual or bisexual sex as a risk factor for HIV infection. The median CD4 lymphocyte count was 19 cells/microliter. The most common symptoms were cough, dyspnea, and fever. Patients with a concurrent opportunistic pneumonia had a higher median serum lactate dehydrogenase (LDH) concentration than did those with pulmonary KS alone (p<0.001). The most common chest radiograph findings were bronchial-wall thickening, nodules, Kerley B lines, and pleural effusions. The presence of granular opacities or cystic spaces usually indicated concomitant Pneumocystitis carinii pneumonia (p < 0.001). Twenty-six patients (15.5%, 95% CI = 10.2% to 20.8%) had pulmonary KS in the absence of mucocutaneous involvement. The presentation of pulmonary KS is characterized by symptoms that cannot be distinguished from those of a superimposed infection. An elevated serum LDH concentration or a chest radiograph with granular opacities or cystic spaces should raise the suspicion of concurrent opportunistic pneumonia. The diagnosis of pulmonary KS should be considered in an HIV-infected homosexual or bisexual male with respiratory symptoms even in the absence of mucocutaneous lesions.

Acquired Immunodeficiency Syndrome

Reliability of anergy skin testing in persons with HIV infection. The pulmonary Complications of HIV Infection Study Group.

Testing with antigens that elicit delayed-type cutaneous hypersensitivity reactions is commonly used to evaluate immune competence in persons infected with the human immunodeficiency virus; however, the reliability of such testing has not been determined. We performed serial testing with tuberculin, mumps, and Candida antigens in 491 HIV-infected persons and found that 30% of persons who initially had no reaction (0 mm) to any of the three antigens, and, thus, were considered to be anergic, had reaction to the mumps or Candida antigen when they were retested 12 months later. We also examined the results of mumps antigen tests in 50 subjects who had a negative tuberculin tests after an initial positive test. The mumps antigen test was positive in 39% of the subjects when the tuberculin test was falsely negative. We conclude that tests commonly used to define anergy cannot reliably identify the anergic state. Moreover, using the mumps antigen to aid in the interpretation of the tuberculin test will often lead to erroneous conclusions. These data indicate that the results of anergy testing should not be used to make individual patient decisions concerning preventive therapy for tuberculosis.

Administration, Cutaneous

Bacterial pneumonia in persons infected with the human immunodeficiency virus. Pulmonary Complications of HIV Infection Study Group.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection are at increased risk for bacterial pneumonia in addition to opportunistic infection. However, the risk factors for bacterial pneumonia and its incidence in this population are not well defined. METHODS: In a multicenter, prospective, observational study, we monitored 1130 HIV-positive and 167 HIV-negative participating adults for up to 64 months for pulmonary disease. The HIV-positive group comprised 814 homosexual or bisexual men, 261 injection-drug users, and 55 female partners of HIV-infected men. RESULTS: There were 237 episodes of bacterial pneumonia among the HIV-positive participants (rate, 5.5 per 100 person-years), as compared with 6 episodes among the HIV-negative participants (rate, 0.9 per 100 person-years; P < 0.001). The rate of bacterial pneumonia increased with decreasing CD4 lymphocyte counts (2.3, 6.8, and 10.8 episodes per 100 person-years in the strata with more than 500, 200 to 500, and fewer than 200 cells per cubic millimeter, respectively; P < or = 0.022 for each comparison). Injection-drug users had a higher rate of bacterial pneumonia than did homosexual or bisexual men or female partners. In the stratum with the fewest CD4 lymphocytes, cigarette smoking was associated with an increased rate of pneumonia. Mortality was almost four times higher among participants with an episode of pneumonia than among the others. Prophylaxis with trimethoprim-sulfamethoxazole was associated with a 67 percent reduction in confirmed episodes of bacterial pneumonia (P = 0.007). CONCLUSIONS: Bacterial pneumonia is more frequent in HIV-positive persons than in seronegative controls, and the risk is highest among those with CD4 lymphocyte counts below 200 per cubic millimeter and among injection-drug users.

AIDS-Related Opportunistic Infections

Mycobacterium avium complex in water, food, and soil samples collected from the environment of HIV-infected individuals.

As part of an epidemiologic study of Mycobacterium avium complex (MAC) infection in San Francisco, water, food and soil samples were collected from the home environment of 290 persons with human immunodeficiency virus (HIV) infection and cultured for mycobacteria. Isolates recovered from the environment were compared with isolates cultured from study patients. Although mycobacteria were recovered from numerous environmental samples, isolates reactive with MAC-specific DNA probes were recovered from only four of 528 (0.76%) water samples and one of 397 (0.25%) food samples. The species M. avium was recovered from one water (0.19%) and one food sample. In contrast, MAC was recovered from 55% and M. avium from 27% of soil samples taken from potted plants in patients' home. Speciation of 76 MAC isolates from study patients showed all isolates belonged to the species M. avium. With use of serotype and multilocus enzyme electrophoresis analysis, some of the soil isolates were found to be similar to isolates recovered from study patients. The results of this study suggest that soil, rather than water, may be a significant reservoir of organisms causing MAC infection in San Francisco.

Bacteriological Techniques

The intrinsic transmission dynamics of tuberculosis epidemics.

In developed countries the major tuberculosis epidemics declined long before the disease became curable in the 1940s. We present a theoretical framework for assessing the intrinsic transmission dynamics of tuberculosis. We demonstrate that it takes one to several hundred years for a tuberculosis epidemic to rise, fall and reach a stable endemic level. Our results suggest that some of the decline of tuberculosis is simply due to the natural behaviour of an epidemic. Although other factors must also have contributed to the decline, these causal factors were constrained to operate within the slow response time dictated by the intrinsic dynamics.

Disease Outbreaks