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Community-Acquired Pneumonia in a Cohort of Former Injection Drug Users With and Without Human Immunodeficiency Virus Infection: Incidence, Etiologies, and Clinical Aspects Antonio Boschini, Camillo Smacchia, Matteo Di Fine, Antonella Schiesari, Paolo Ballarini, Massimo Arlotti, Chiara Gabrielli, Gastone Castellani, Mariagrazia Genova, Paolo Pantani, Alessandro Cozzi Lepri, and Giovanni Rezza
From San Patrignano Centro Medico and Ospedale di Rimini (Dipartimento Malattie Infettive), Rimini; and Centro Operativo AIDS (Laboratorio di Epidemiologia e Biostatistica) and Istituto Superiore di Sanita, Rome. Italy
Injection-drug use and HIV infection are considered to be two independent risk factors for acute bacterial pneumonia [14]. The increased susceptibility to pneumonia of injection-drug users (IDUs) may be explained by several factors. Specifically, denutrition and continuous antigenic stimulations may weaken these individuals' immune systems, whereas poor oral hygiene, narcosis, and pulmonary takosis may predispose them to respiratory infections. There are also the deleterious effects of opiates on lung defenses and cough reflexes [5]. During the 1980s, a great increase in deaths and hospitalizations from pneumonia was observed among IDUs in New York City [6-8], inciting researchers to design studies for estimating the incidence of pneumonia among HIV-positive and -negative drug users and to study the correlation between HIV-induced immune suppression and the risk of pneumonia due to various etiologies [1, 9]. One of these studies showed that the annual risks of community-acquired pneumonia were 2.1% and 9.7% for HIV-seronegative and HIV-seropositive active IDUs, re-
Received 13 March 1995; revised 11 March 1996. Presented in part at the 4th European Conference on Clinical Aspects and Treatment of HIV Infection [abstract no. 279], held in Milan in March 1994. Reprints or correspondence: Dr. Antonio Boschini, San Patrignano Medical Center, San Patrignano, 47040 Coriano (Rimini), Italy. Clinical Infectious Diseases
1996;23:107-13
© 1996 by The University of Chicago. All rights reserved. 1058-4838/96/2301-0015$02.00
spectively [1], compared with a risk of 0.3% in the general population [10]. Because of the excessive rates of morbidity and mortality associated with pneumonia in IDUs [6, 9], recurrent pneumonia has been included as an AIDS-defining criterion since 1993 [11]. In addition to the increased incidence of pneumonia among HIV-infected persons, these patients are at higher risk for bacteremic infections and recurrences [2, 12]. Encapsulated bacteriamost commonly Streptococcus pneumoniae [12-17], followed by Haemophilus influenzae [18, 19]-are the leading cause of pneumonia in both HIV-positive and HIV-negative persons. Although the association among bacterial pneumonia, HIV infection, and injection-drug use is becoming clearer, there is still a need for community-based studies to estimate the risk of community-acquired pneumonia among HIV-positive and HIV-negative IDUs. Furthermore, little information is available on the incidence and clinical aspects of the so-called atypical pneumonias, particularly those caused by Mycoplasma pneumoniae and Chlamydia pneumoniae, in HIV-positive patients at various stages of the disease. We report the findings of a prospective study of a large number of former IDUs living in a residential community; the aim of this study was to estimate the incidence of communityacquired pneumonias of different etiologies and to evaluate the impact of HIV infection and HIV-related immune dysfunction on the risk of developing acute bacterial pneumonia and atypical pneumonia.
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Although the association among bacterial pneumonia, human immunodeficiency virus (HIV) infection, and injection-drug use seems to have been well established, accurate estimates of the risk of communityacquired pneumonia among HIV-positive and Hlv-negative injection-drug users (IDUs) are still needed. To estimate the incidence of pneumonia in a community of former IDUs, we followed 4,236 persons between 1991 and 1994; 1,114 (26.3%) were HIV-positive and 3,122 (73.7%) were HIV-negative. All patients were evaluated for pneumonia by standard criteria, a serum sample was obtained from each participant at least once a year, and laboratory values were monitored. Overall, 149 episodes of pneumonia occurred among mv-positive patients and 61 among HIV -negative patients; incidence rates were 90.5 and 14.2 (per 1,000 person-years), respectively. The most common etiologic agents were Streptococcuspneumoniae, Chlamydia pneumoniae, and Haemophilus influenzae. Among the HIV-positive former IDUs, there was a 1.37-fold increase in the relative risk of pneumonia for every decrease of 100/mm 3 in the CD4 cell count (95% confidence interval, 1.16-1.61). The incidence of community-acquired pneumonia was markedly higher among HIV-positive participants than among Hlv-negative ones, a finding similar to that concerning the general population.
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Methods Study Site
Study Population
All IDUs entering the community between 1 January 1991 and 31 December 1994 were included in the study. At least once a year, a serum sample from each participant was obtained and stored. The community rules prohibit the use of illicit or psychotropic drugs, but all of the patients were smokers and were allowed a maximum of 10 cigarettes a day. One glass of wine per meal was also allowed. In accordance with the San Patrignano Medical Center protocol, all entering drug users underwent a physical examination, chest roentgenography, electrocardiography, intradermal PPD (5 IU) testing, delayed skin testing (Multi-Merieux; Institut Merieux, Lyon, France), and routine blood analyses, including serology for HIV, hepatitis Band C viruses, and Treponema pallidum. For HIV-infected patients, lymphocyte-subset determinations, further serologies (for human T-cell leukemia virus 1, Toxoplasma gondii, and cytomegalovirus), and abdominal echography were also performed. For any type of medical problem, residents were sent to the community's medical center, which includes an outpatient facility, a day-hospital unit, and a 50-bed ward. Preventive treatment with isoniazid is routinely administered for 12 months to PPD-positive (area of induration, >5 mm), HIVpositive individuals whose CD4 lymphocyte count falls below 500/mm 3 • Chemoprophylaxis for other opportunistic infections is administered on the basis of standard criteria. In autumn, influenza vaccination is offered to all residents (mean acceptance rate, 50%). Diagnostic Procedures
All patients with an acute respiratory illness more serious than a common cold or with a fever (temperature, >38°C) lasting> 3 days underwent medical examination. For suspected lower respiratory tract infections, additional investigations included chest roentgenography, sputum examination, blood culture, and arterial blood gas analysis. When necessary, sputum specimens were obtained with hypertonic saline aerosol induction. Only sputum specimens of good quality (> 10 polymorphonuclear leukocytes per squamous cell) were accepted, and
diagnosis was based on concordance between microscopic findings and culture results. For all diagnosed cases, blood samples were drawn at the onset of symptoms and after 30 and 60 days and stored at - 30°C. Laboratory values pertaining to erythrocyte sedimentation, C-reactive protein, total WBCs (with differential), iron, creatinine, electrolytes, and lactate dehydrogenase were determined at the time the first serum sample was obtained. In cases of clinical or radiological diagnosis ofpneumonia, convalescent serum samples were assayed for antibodies to M pneumoniae (by indirect agglutination), Legionella species (ELISA for IgG and IgM), C. pneumoniae (microimmunofluorescence for IgG and IgM), Q fever (microimmunofluorescence for IgG and IgM to Coxiella burnetii phases 1 and 2 antigen), and adenovirus (ELISA for IgG and IgM). Acute-phase sera were tested only when the convalescent sera were significantly positive. A fourfold increase in IgG antibody titer, a single IgG titer of I :512, or a single IgM titer of 1:16 was considered diagnostic for C. pneumoniae infection, in accordance with the international literature [20]. Respiratory opportunistic infections were diagnosed with use of criteria recommended by the Centers for Disease Control and Prevention [21].
Criteria for Inclusion
Community-acquired pneumonia was diagnosed on the basis of a new pathological finding on a chest roentgenogram and the occurrence of new respiratory and/or systemic symptoms.
Criteria for Exclusion
Former IDUs with recurrent lower respiratory tract infections due to bronchiectasis-which have been reported to be more common among HIV-positive persons [22]-and those with nosocomial pneumonia were excluded from analysis. Patients with opportunistic respiratory infections listed in the 1987 case definition for AIDS [21] were also excluded.
Statistical Analysis
The frequency of symptoms by etiologic agent and HIV serostatus was calculated. Differences were evaluated by X2 and Wilcoxon's tests, and resulting P values were reported when they were 500/mm' L __1
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