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P C Hopewell

Publications and source records attributed to P C Hopewell.

At least 19 recordsLinked to original sources

Pneumococcal disease during HIV infection. Epidemiologic, clinical, and immunologic perspectives.

OBJECTIVE: To characterize the epidemiology, clinical manifestations, and immunologic risk factors for infections with Streptococcus pneumoniae among persons infected with human immunodeficiency virus (HIV); and to delineate a practical approach for diagnosis, treatment, and prevention of these infections. DATA SOURCES: English-language articles from Index Medicus and their references as well as abstracts from conference proceedings that compared rates as well as clinical and microbiologic features of S. pneumoniae infections in HIV-infected patients. STUDY SELECTION: All human studies that included denominators, appropriate control groups, or sufficient clinical descriptions and animal studies with key immunologic observations were cited. DATA EXTRACTION: We compared epidemiologic and clinical responses to pneumococcal disease in HIV-infected patients and control subjects and correlated clinical and experimental data on immunologic defects associated with HIV infection with those on regulation of pneumococcal infections. DATA SYNTHESIS: Among patients with HIV infection, the incidence of invasive pneumococcal disease is high, bacteremia is a common complication of pneumonia, and relapses occur frequently. However, the clinical presentation, response to therapy, and serotypes isolated are similar to those in persons without HIV infection, and mortality is similar or lower. Specific local and systemic defects in host defense, particularly humoral immunity, may contribute to the high incidence of invasive pneumococcal disease. CONCLUSIONS: Streptococcus pneumoniae is the leading cause of invasive bacterial respiratory disease in adults and children with HIV infection. Prompt diagnosis and antimicrobial therapy are associated with a favorable clinical outcome. Characterizing the specific immunologic defects associated with invasive pneumococcal disease in HIV-infected patients may facilitate development of successful, cost-effective strategies for prophylaxis.

HIV Infections

An outbreak of tuberculosis with accelerated progression among persons infected with the human immunodeficiency virus. An analysis using restriction-fragment-length polymorphisms.

BACKGROUND: Tuberculosis typically develops from a reactivation of latent infection. Clinical tuberculosis may also arise from a primary infection, and this is thought to be more likely in persons infected with the human immunodeficiency virus (HIV). However, the relative importance of these two pathogenetic mechanisms in this population is unclear. METHODS: Between December 1990 and April 1991, tuberculosis was diagnosed in 12 residents of a housing facility for HIV-infected persons. In the preceding six months, two patients being treated for tuberculosis had been admitted to the facility. We investigated this outbreak using standard procedures plus analysis of the cultured organisms with restriction-fragment-length polymorphisms (RFLPs). RESULTS: Organisms isolated from all 11 of the culture-positive residents had similar RFLP patterns, whereas the isolates from the 2 patients treated for tuberculosis in the previous six months were different strains. This implicated the first of the 12 patients with tuberculosis as the source of this outbreak. Among the 30 residents exposed to possible infection, active tuberculosis developed in 11 (37 percent), and 4 others (13 percent) had newly positive tuberculin skin tests. Of 28 staff members with possible exposure, at least 6 had positive tuberculin-test reactions, but none had tuberculosis. CONCLUSIONS: Newly acquired tuberculous infection in HIV-infected patients can spread readily and progress rapidly to active disease. There should be heightened surveillance for tuberculosis in facilities where HIV-infected persons live, and investigation of contacts must be undertaken promptly and be focused more broadly than is usual.

Adult

Impact of human immunodeficiency virus infection on the epidemiology, clinical features, management, and control of tuberculosis.

After years of decreasing prevalence and increasing hope that tuberculosis, like smallpox, could be eliminated, the disease has resurfaced as a major public health problem in the United States. Particularly ominous are the appearance of multiple-drug-resistant strains and their impact on patients and health care workers who are infected with the human immunodeficiency virus, among whom mortality rates reach 80% 2-3 months postdiagnosis. To respond effectively to this new threat, it is critical that we reorient our thinking about tuberculosis and redirect health care resources to programs for tuberculosis control. We need to reinstitute screening of high-risk populations and ensure proper isolation of patients with the disease. Diagnosing tuberculosis at the earliest possible stage is obviously of the utmost importance. High priority must be given to the development of rapid diagnostic tests and techniques that screen for drug resistance. We must implement and adequately fund drug-discovery programs to develop new therapeutic agents that are effective against multiple-drug-resistant strains of Mycobacterium tuberculosis. Effective programs for monitoring the treatment of patients with tuberculosis must also be implemented. Failure to adequately support such programs has probably led to the recent upswing in multiple-drug-resistant tuberculosis, especially in large cities along the eastern seaboard. Leadership for and funding of these programs must come from the federal government, specifically the U.S. Department of Health & Human Services and the Centers for Disease Control (Atlanta). The Infectious Diseases Society of America is actively supporting a variety of tuberculosis control-related initiatives and will keep its members updated on progress in this area.(ABSTRACT TRUNCATED AT 250 WORDS)

HIV Infections

Effect of aerosolized pentamidine prophylaxis on the clinical severity and diagnosis of Pneumocystis carinii pneumonia.

To determine if the use of aerosolized pentamidine prophylaxis decreases the clinical severity or the sensitivity of diagnostic tests for Pneumocystis carinii pneumonia (PCP), we conducted a retrospective matched cohort comparison study of patients admitted to San Francisco General Hospital with PCP from August 1, 1989, to June 30, 1990. Patients who had received pentamidine prophylaxis during at least the 2 months prior to the diagnosis of PCP were matched with patients who had not received the drug. Matching was based on the number of prior episodes of PCP, sex, age, and risk factors for human immunodeficiency virus infection. As markers of clinical severity, we chose alveolar-arterial oxygen difference, serum lactate dehydrogenase levels, outpatient versus inpatient treatment, length of hospitalization, length of intravenous anti-pneumocystis treatment, development of respiratory failure, in-hospital mortality, and chest radiographic appearance. Although, of the 27 matched pairs identified, significantly fewer of the pentamidine cohort were treated as inpatients, and significantly more of this cohort had upper lobe dominant disease on chest radiograph, we found no other significant differences between markers of clinical severity for the two cohorts. In addition, we found no significant differences in the rate of sputum or bronchoalveolar lavage positivity for P. carinii between the two cohorts. We conclude that, although hospitalization is less common in patients with a history of prophylactic pentamidine use, aerosolized pentamidine prophylaxis does not decrease the clinical severity or the sensitivities of sputum induction or bronchoalveolar lavage as diagnostic tests for PCP.

AIDS-Related Opportunistic Infections

Toxoplasma gondii pneumonitis in patients infected with the human immunodeficiency virus.

Pulmonary toxoplasmosis is a rarely recognized opportunistic infection in immunocompromised patients. A few case reports have described pulmonary toxoplasmosis in human immunodeficiency virus-infected patients in association with Toxoplasma gondii central nervous system disease. We encountered six cases of pulmonary toxoplasmosis in human immunodeficiency virus-infected patients who presented with a protracted febrile illness, respiratory symptoms, and an abnormal chest roentgenogram in the absence of neurologic findings. No clinical or roentgenographic features distinguished T gondii pneumonitis from more common opportunistic pulmonary infections. As the acquired immunodeficiency syndrome epidemic progresses, the presenting illnesses have evolved. Toxoplasma gondii must be considered a potential cause of pulmonary disease during the evaluation of human immunodeficiency virus-infected patients with respiratory symptoms.

Acquired Immunodeficiency Syndrome

Treatment of tuberculosis in patients with advanced human immunodeficiency virus infection.

BACKGROUND AND METHODS: Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988. RESULTS: At the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid-fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3. CONCLUSIONS: Tuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse.

Acquired Immunodeficiency Syndrome

Natural history of disseminated Mycobacterium avium complex infection in AIDS.

This study sought to better characterize the natural history of AIDS-associated disseminated Mycobacterium avium complex (MAC) infection. Towards that end two retrospective studies were done: a case-control survival study and a MAC respiratory colonization study. Among 137 consecutive patients who had a sterile body site cultured for mycobacteria within 3 months of their first AIDS-defining episode of Pneumocystis carinii pneumonia, median survival was significantly shorter in those with disseminated MAC infection (107 days; 95% confidence interval [CI] 55-179) than those with negative cultures (275 days; 95% CI 230-318; P less than .01), even after controlling for age, absolute lymphocyte count, and hemoglobin concentration. Among 34 patients with AIDS and respiratory MAC colonization, 22 later developed disseminated infection (65% predictive value for subsequent MAC dissemination). Disseminated MAC infection was associated with significantly shorter survival for patients with AIDS, and the presence of MAC in respiratory specimens has substantial predictive value for subsequent disseminated infection.

Acquired Immunodeficiency Syndrome

Pneumocystis carinii pneumonia and respiratory failure in AIDS. Improved outcomes and increased use of intensive care units.

To determine whether the outcome of intensive care for patients with AIDS, Pneumocystis carinii pneumonia (PCP), and respiratory failure has changed, we studied patients admitted to the intensive care units an San Francisco General Hospital from 1981 to 1988. We compared the course of patients with PCP and respiratory failure admitted to the intensive care unit from 1986 to 1988 with a similar cohort hospitalized from 1981 to 1985. The hospital survival rate for the 35 patients in the 1986 to 1988 cohort was 40%, compared with 14% for the 42 patients in the 1981 to 1985 cohort (p less than 0.01). Age, episode of PCP, time since AIDS diagnosis, anti-PCP therapy, and important clinical variables were similar in both cohorts. Corticosteroids were used commonly in the recent era. Patients who received steroids had an in-hospital survival rate of 46%, compared with 22% for those who did not receive steroids (p = NS). In a stepwise logistic regression model, ICU care in the recent era and higher serum albumin at the time of ICU admission were the only variables significantly associated with survival. The hospital survival of patients with PCP and respiratory failure has improved. The improvement could not be explained by patient selection or by better anti-PCP therapy. The apparent beneficial effect of corticosteroids deserves further study. The improvement in ICU outcome was reflected in increased ICU utilization by patients with AIDS, PCP, and respiratory failure.

Acquired Immunodeficiency Syndrome

Morbidity and mortality of patients with AIDS and first-episode Pneumocystis carinii pneumonia unaffected by concomitant pulmonary cytomegalovirus infection.

To determine the significance of cytomegalovirus (CMV) pulmonary coinfection with Pneumocystis carinii pneumonia in AIDS, we examined the association of long- and short-term survival and morbidity (as defined by length of hospital stay) with recovery of CMV from bronchoscopy specimens and an indirect measure of virus titer in bronchoalveolar lavage fluid (the time to develop CMV cytopathology in culture) in 111 patients diagnosed with a first episode of P. carinii pneumonia. Compared with 57 individuals from whom CMV was not isolated, the 54 individuals from whom CMV were isolated did not differ in baseline characteristics, long-term survival (213 versus 275 days, p = 0.97), acute death rate (19% in both, p = 1.0), or length of hospital stay (19.7 versus 21.1 days, p = 0.68). Also, the time to develop CMV cytopathology in culture did not correlate with acute or long-term survival. Our observations thus do not support the use of CMV-specific antiviral therapy in AIDS patients with P. carinii pneumonia who also have evidence of pulmonary CMV infection.

Acquired Immunodeficiency Syndrome

Stability of positive tuberculin tests: are boosted reactions valid?

To determine the stability and presumed significance of tuberculin skin tests, we followed a cohort of 380 tuberculin-positive patients living in chronic care facilities. Each patient had a positive reaction (greater than or equal to 10 mm induration to 5 tuberculin units of purified protein derivative) to one of three sequential baseline tuberculin tests. One year after the initial series, each patient had a single repeat skin test. Reversion to a negative test occurred in 98 (26%) of the 380 patients. Decreases in induration of 6 mm or more occurred in 88 (90%) of the reverters. Initially positive tests were more likely (p less than 0.001) to remain stable than tests that were "boosted" to positive reactions on the second or third initial administration. Stable responses were found in 96% of those whose tests had greater than or equal to 15 mm induration compared with 61% of those with reactions of 10 to 14 mm induration. Increasing age also was associated with a high rate of reversion. The instability of boosted tuberculin reactions brings into question the clinical significance of these tests. We propose limiting tuberculin testing to two sequential tests.

Aged

Clinical features, diagnoses, and management of tuberculosis in immunocompromised hosts.

For many years tuberculosis has been known to occur with greater frequency among persons with disorders that impair host defenses. In most instances these processes interfere with the immune response to Mycobacterium tuberculosis, whereas, in a few, such as silicosis, the probable abnormality is a nonimmune defect in macrophage function. Infection with the human immunodeficiency virus (HIV) causes progressive and ultimately profound depression of both humoral and cell-mediated immunity and, thus, is an extremely potent risk-factor for tuberculosis. Presumably the major effect of HIV infection that predisposes persons to developing tuberculosis is the reduction in circulating T-helper (CD4+) lymphocytes which causes a reduction in cytokine production and a consequent decrease in the functional capabilities of macrophages. However, a number of questions concerning pathogenesis of tuberculosis related to HIV remain. Available data suggest that the magnitude of the risk for developing tuberculosis among persons infected with both HIV and M. tuberculosis is very high, 8% in one prospective study. Because of the epidemic of HIV infection, the progressive downward trend in the incidence of tuberculosis in the United States has reversed and in 1989 there was a 5% increase in the number of cases. Preliminary data for 1990 suggest that there will be an 8 to 10% increase over 1989. Also in the United States approximately 3% of tuberculosis patients have been found to be HIV seropositive. The clinical features of tuberculosis in patients with HIV infection vary depending on the degree of immunosuppression. With mild immunosuppression early in the course of HIV infection tuberculosis presents in a "typical" way with positive tuberculin skin tests, upper lobe cavitary infiltrates on chest film and positive sputum smears and cultures. As the HIV infection progresses, the mode of presentation of tuberculosis becomes more "atypical" with negative skin tests, multiple sites of involvement, chest films showing diffuse noncavitary infiltrates often accompanied by intrathoracic lymphadenopathy. The key to diagnosis is maintaining a high index of suspicion for tuberculosis, especially in patients with advanced HIV disease and including appropriate laboratory examinations in the evaluations of such persons. Regardless of the stage of HIV infection the response to treatment for tuberculosis is generally favorable if it is begun promptly. Standard therapy utilizing isoniazid, rifampin, and pyrazinamide with or without ethambutol have been associated with high rates of cure. Relapse has been uncommon. There has been, however, at least one outbreak of tuberculosis caused by isoniazid and rifampin resistant organisms in which the response to therapy was very poor.(ABSTRACT TRUNCATED AT 400 WORDS)

HIV Infections

Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone.

BACKGROUND: Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic. METHODS: In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P. carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day). RESULTS: The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3). Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025). With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs. one). Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations. Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient. Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone. CONCLUSIONS: In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P. carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.

Acquired Immunodeficiency Syndrome

Human immunodeficiency virus infection in tuberculosis patients.

Human immunodeficiency virus (HIV) serology was performed in non-Asian-born patients 18-65 years old with newly diagnosed tuberculosis at a county tuberculosis clinic, and demographic and clinical features of HIV-seropositive and HIV-seronegative patients were compared. Sixty of 128 eligible patients agreed to participate, of whom 17 (28%) were seropositive. Risk of HIV was associated with homosexual contact, intravenous drug use, or both; however, 4 (24%) of the 17 seropositives denied risk behaviors. Significantly more blacks (48%) than whites (10%) or Latinos (20%) were HIV-seropositive (P less than .01). Site of disease, tuberculin reactivity, response to therapy, drug toxicity, and relapse did not differ significantly between groups. HIV-seropositive patients had significantly lower median CD4+ cell counts (326/mm3, range 23-742/mm3, vs. 929/mm3, range 145-2962/mm3, P less than .0005) and median CD4+:CD8+ ratios (0.50, range 0.14-1.07 vs. 1.54, range 0.35-4.36, P less than .0001). HIV infection is associated with clinically typical tuberculosis and HIV screening of tuberculosis patients is recommended in areas where HIV is endemic.

Acquired Immunodeficiency Syndrome

Why tuberculosis is not prevented.

Because of the effectiveness of isoniazid in treating tuberculosis infection, progression to tuberculosis should be largely preventable. Thus, each case of tuberculosis that occurs may be viewed as a "failure" of the prevention system. We studied the reasons for these "failures" at three centers in different geographic areas in the United States. Two hundred seventy-nine patients with bacteriologically confirmed tuberculosis were evaluated by means of a questionnaire. Our results suggest three main reasons for these missed opportunities of tuberculosis prevention. (1) Patients are out of the health care system until they develop tuberculosis. (2) Patients are in the system but are either not screened for tuberculous infection or, if screened, are not offered preventive therapy when it is appropriate. (3) Because of false negative skin test results, screening may be ineffective at the time it is applied. Advances in tuberculosis prevention will require attention to these areas.

Adolescent

Comparative recovery of cytomegalovirus from saliva, mucolysed induced sputum, and bronchoalveolar lavage fluid from patients at risk for or with acquired immunodeficiency syndrome.

The recovery rates of cytomegalovirus from mucolysed induced sputum samples and bronchoalveolar lavage fluid obtained from individuals at risk for or with acquired immunodeficiency syndrome were compared. It was demonstrated that cytomegalovirus could be reliably recovered from mucolysed induced sputum, and such recovery was highly predictive of recovery from bronchoalveolar lavage samples obtained from the same individual.

Acquired Immunodeficiency Syndrome

Prevention of lung infections associated with human immunodeficiency virus infection.

Current evidence indicates that the length of survival for patients with the acquired immunodeficiency syndrome (AIDS) is increasing, thereby affording a greater opportunity for strategies designed to prevent the infectious diseases that mark the syndrome. Because these infections may occur at different stages of immunosuppression caused by the human immunodeficiency virus (HIV), effective application of preventive measures depends not only on detection of HIV infection but also on the use of staging indicators. The diseases that serve to define AIDS, such as Pneumocystis carinii pneumonia, tend to occur late in the course of HIV infection and often when the T helper lymphocyte (CD4+ cells) count is less than 0.2 x 10(9)/l. Other infections, such as tuberculosis and pyogenic bacterial pneumonia, may develop at any point after HIV infection has occurred. Given this relation between the degree of immunosuppression and the occurrence of particular pulmonary infections, different preventive interventions should be applied at different times. It is now known that the incidence of several of the pulmonary infections that are common in patients with HIV infection can be reduced by prophylactic measures. Pneumocystis pneumonia is decreased in frequency by any one of several prophylactic agents, the best established being pentamidine administered as an inhaled aerosol. The role of isoniazid in the chemoprophylaxis of tuberculosis in patients not infected with HIV is well established. Although there is little evidence of benefit so far from isoniazid in HIV infected patients with a positive tuberculin skin test response, it is logical to assume that there could be some effect. The use of pneumococcal polysaccharide vaccine may also be of some benefit in reducing the frequency of pneumococcal pneumonia in patients with AIDS. In addition to these specific measures, the antiretroviral agent zidovudine decreases both the frequency and the severity of opportunist infections, at least during the first few months of treatment. A comprehensive strategy for prevention of HIV associated lung infection first requires detection of HIV seropositivity, staging the immunosuppression by the CD4+ cell count, and determining whether tuberculous infection is present by a tuberculin skin test. All seropositive individuals should be given pneumococcal vaccine and those with evidence of tuberculosis infection should be treated with isoniazid for one year. Zidovudine should probably be started when CD4+ cell counts are in the range 0.4-0.5 x 10(9)/l and prophylaxis against pneumocystis infection when CD4+ cell counts are in the range 0.2-0.3 x 10(9)/l.

Acquired Immunodeficiency Syndrome