Crack cocaine and infectious tuberculosis.We hypothesize hy·poth·e·size v. hy·poth·e·sized, hy·poth·e·siz·ing, hy·poth·e·siz·es v.tr. To assert as a hypothesis. v.intr. To form a hypothesis. that crack cocaine is independently associated with smear-positive tuberculosis (TB). In a case-control study case-control study, n an investigation employing an epidemiologic approach in which previously existing incidents of a medical condition are used in lieu of gathering new information from a randomized population. of TB in London, 19 (86%) of 22 crack cocaine users with pulmonary TB pulmonary TB Pulmonary tuberculosis, see there were smear positive compared with 302 (36%) of 833 non-drug users. Respiratory damage caused by crack cocaine may predispose pre·dis·pose v. To make susceptible, as to a disease. drug users to infectivity. ********** Tuberculosis (TB) has reemerged as a public health problem in London, and drug users are at high risk of contracting and spreading the disease (1). The United Kingdom has seen a substantial increase in the prevalence of drug use in the past decade, particularly crack cocaine use (2). Numbers of crack cocaine users assessed while in police custody in London increased 3-fold from 1993 through 2003 (3). There are an estimated 46,000 crack cocaine users in London; most also use opiates Opiates Analgesic, pain killing drugs, such as heroin and morphine that depress the central nervous system. Mentioned in: Withdrawal Syndromes (4). Evidence to directly link risk for TB with crack cocaine use is lacking, although an association with tuberculin tuberculin /tu·ber·cu·lin/ (-lin) a sterile solution containing the growth products of, or specific substances extracted from, the tubercle bacillus; used in various forms in the diagnosis of tuberculosis; see also under test. positivity has been shown. Increased exposure risk is considered largely attributable to social and lifestyle factors including homelessness, imprisonment Imprisonment See also Isolation. Alcatraz Island former federal maximum security penitentiary, near San Francisco; “escapeproof.” [Am. Hist.: Flexner, 218] Altmark, the German prison ship in World War II. [Br. Hist. , and drug and alcohol abuse (5). Drug users are commonly immunocompromised immunocompromised /im·mu·no·com·pro·mised/ (-kom´pro-mizd) having the immune response attenuated by administration of immunosuppressive drugs, by irradiation, by malnutrition, or by certain disease processes (e.g., cancer). through HIV HIV (Human Immunodeficiency Virus), either of two closely related retroviruses that invade T-helper lymphocytes and are responsible for AIDS. There are two types of HIV: HIV-1 and HIV-2. HIV-1 is responsible for the vast majority of AIDS in the United States. infection and malnutrition, resulting in increased risk for TB infection and rapid progression to active disease. Habitually smoking crack cocaine causes pulmonary damage (crack lung) (Figure). Consequently, alveolar macrophage alveolar macrophage n. A vigorously phagocytic macrophage on the epithelial surface of lung alveoli that ingests carbon and other inhaled particulate matter. Also called coniophage, dust cell. function and cytokine Cytokine Any of a group of soluble proteins that are released by a cell to send messages which are delivered to the same cell (autocrine), an adjacent cell (paracrine), or a distant cell (endocrine). production is impaired, which may enhance susceptibility to infectious diseases (6). Mycobacterium tuberculosis Mycobacterium tuberculosis n. Tubercic bacillus. Mycobacterium tuberculosis is an intracellular pathogen that begins the disease process after a person inhales bacilli bacilli /ba·cil·li/ (bah-sil´i) plural of bacillus. bacilli see bacillus. into the terminal bronchi bronchi /bron·chi/ (brong´ki) plural of bronchus. Bronchi Two main branches of the trachea that go into the lungs. This then further divides into the bronchioles and alveoli. and pulmonary alveoli Alveoli Small air sacs or cavities in the lung that give the tissue a honeycomb appearance and expand its surface area for the exchange of oxygen and carbon dioxide. (7). Alveolar alveolar /al·ve·o·lar/ (al-ve´o-lar) [L. alveolaris ] pertaining to an alveolus. al·ve·o·lar adj. Relating to an alveolus. epithelial cells Epithelial cells Cells that form a thin surface coating on the outside of a body structure. Mentioned in: Corneal Transplantation likely resist invasion by M. tuberculosis M. tuberculosis, n the bacterium responsible for tuberculosis, generally a respiratory infection in man; nonrespiratory tuberculosis is considered an indicator disease for AIDS. See also tuberculosis. bacilli, enabling resident alveolar macrophages and dendritic cells sufficient time to traverse the epithelium and phagocytose phag·o·cy·tose v. To phagocytize. phagocytose to envelop and destroy bacteria and other foreign material; phagocytize. potential invading microbes (8). Several pulmonary complications are associated with the inhalation of crack cocaine (e.g., intensive cough, hemoptysis Hemoptysis Definition Hemoptysis is the coughing up of blood or bloody sputum from the lungs or airway. It may be either self-limiting or recurrent. Massive hemoptysis is defined as 200-600 mL of blood coughed up within a period of 24 hours or less. , shortness of breath Shortness of Breath Definition Shortness of breath, or dyspnea, is a feeling of difficult or labored breathing that is out of proportion to the patient's level of physical activity. , chest pain, acute bilateral pulmonary infiltrates, thermal airway injury, pneumothorax pneumothorax (n  mōthôr`ăks), collapse of a lung with escape of air into the pleural cavity between the lung and the chest wall. The cause may be traumatic (e.g. and noncardiogenic pulmonary edema Pulmonary Edema DefinitionPulmonary edema is a condition in which fluid accumulates in the lungs, usually because the heart's left ventricle does not pump adequately. , production of carbonaceous car·bo·na·ceous adj. Consisting of, containing, relating to, or yielding carbon. carbonaceous Adjective of, resembling, or containing carbon Adj. 1. sputum sputum /spu·tum/ (spu´tum) [L.] expectoration; matter ejected from the trachea, bronchi, and lungs through the mouth. sputum cruen´tum bloody sputum. , and exacerbation of asthma) (9). Collectively, these complications have been reported as crack syndrome (10). We hypothesize that crack cocaine use increases the risk for smear-positive pulmonary TB and that a component of this risk relates to lung damage caused by crack cocaine inhalation. The Study Detailed clinical and social data were collected by case managers for all TB patients undergoing treatment in London on July 1, 2003. The study was approved by the Metropolitan Multicentre Research Ethics Committee-United Kingdom. Analyses were restricted to pulmonary patients 15-60 years of age (n = 970). We used univariate analyses to compare the characteristics of crack cocaine users, other hard-drug users (predominantly heroin users but excluding those who used only alcohol and marijuana), and those not known to use drugs. A separate category was included for hard-drug users not known to use crack cocaine to have a group with comparable levels of social deprivation, addiction related problems, and difficulty in accessing health services health services Managed care The benefits covered under a health contract . To test the hypothesis that smear positivity at diagnosis was associated with crack cocaine use, we used a multivariate model with backwards elimination to exclude variables that did not make a significant contribution to the model. Variables initially included are shown in Table 1; the final model is shown in Table 2. TB patients who used crack cocaine were predominantly 20-49 years of age. Crack cocaine users and other drug users were significantly more likely than non-drug users to have been born in the United Kingdom, of white or black Caribbean ethnic origin, homeless, alcohol abusers, or have a history of imprisonment. Non-crack drug users tended to have the longest delays between diagnosis and treatment and crack users the shortest, but this tendency did not reach significance (Table 1). Crack cocaine users were statistically significantly more likely to seek treatment at emergency departments, to adhere poorly to treatment regimen, or default from treatment altogether. Drug users were also more likely to have isoniazid-resistant disease. Among crack cocaine users this was primarily related to a large outbreak of isoniazid-resistant TB (11). [FIGURE OMITTED] Among crack cocaine users, diagnosis showed that 86% were smear positive compared with 36% of patients not known to use drugs (relative risk [RR] 2.4, 95% confidence interval confidence interval, n a statistical device used to determine the range within which an acceptable datum would fall. Confidence intervals are usually expressed in percentages, typically 95% or 99%. [CI] 2.0-2.9), p<0.001) and 59% of drug users not known to use crack cocaine (RR 1.6, 95% CI 1.4-2.0, p<0.001). Multivariate analysis multivariate analysis, n a statistical approach used to evaluate multiple variables. multivariate analysis, n a set of techniques used when variation in several variables has to be studied simultaneously. showed that the risk for smear-positive disease was higher for drug users than for those not known to use drugs (odds ratio [OR] 1.9, 95% CI 1.2-3.0, p = 0.007) and highest in crack cocaine users (OR 6.6, 95% CI 1.8-24.3, p = 0.005). Other significant risk factors for smear positivity were being of black Caribbean ethnicity, having multidrug-resistant disease, and seeking treatment at an emergency department. When the multivariate model was restricted to include only hard-drug users, crack cocaine users were still significantly more likely than other drug users to be smear positive (p = 0.02). Conclusions Smear-positive disease is 2.4 times more likely to be diagnosed in crack cocaine users than in non-drug users, whereas hard-drug users not known to use crack cocaine are 1.6 times more likely to be diagnosed with smear-positive disease. Crack cocaine users were significantly more likely than other drug users to be smear positive on diagnosis. The increased risk for smear-positive disease in crack cocaine users was not due to diagnostic delays. Hard-drug users who were not confirmed as crack cocaine users had the longest diagnostic delays. Crack cocaine users had the shortest diagnostic delays, potentially attributable to rapidly progressive, debilitating de·bil·i·tat·ing adj. Causing a loss of strength or energy. Debilitating Weakening, or reducing the strength of. Mentioned in: Stress Reduction disease. Crack cocaine users were also more likely to seek treatment at an emergency department rather than primary care services. Again, the choice of healthcare service may be related to the severity of disease. Symptom duration before diagnosis is difficult to measure, especially among drug users. We included non-crack drug users as a comparison group because they have a similar social profile and similar access to healthcare. Therefore, we are confident that the extremely high levels of smear positivity on diagnosis in crack cocaine users are not due to a long duration of clinical illness preceding diagnosis. In the multivariate model, crack cocaine use remains strongly associated with smear-positive disease after controlling for a wide variety of other potential confounders. Other risk factors include ethnicity (drug use was common among black Caribbean patients and may have been underreported); treatment at an emergency department (possibly a marker of disease severity); and multidrug-resistant disease. We are uncertain why multidrug-resistant cases were more likely to be smear-positive on diagnosis; however, previous studies have found that cavitary disease is a risk factor for drug resistance (12). The fact that smear positivity was significantly more prevalent in patients known to use crack cocaine when compared with other hard-drug users suggests that this additional risk may be attributable to a biological component. Plausible biological mechanisms to explain the increased risk of smear-positive disease include poor alveolar macrophage antimicrobial activity in crack cocaine users due to decreased inducible nitric oxide synthase The nitric oxide synthase (NOS; EC 1.14.13.39) is an enzyme in the body that contributes to transmission from one neuron to another, to the immune system and to dilating blood vessels. activity (13) and direct effects on the lung (10). It is likely that a proportion of hard-drug users were incorrectly classified as not using crack cocaine due to nondisclosure. This would reduce the apparent differences in levels of smear positivity between the groups. Nevertheless, despite relatively small numbers of known crack cocaine users, there is a significantly (p = 0.02) higher proportion of smear-positive disease in these patients compared with other hard-drug users. Previous studies have shown TB transmission associated with crack cocaine use (14). Persons frequenting crack houses are likely to have multiple risk factors for active pulmonary TB. Prolonged sharing of closed and confined airspace, intensive coughing, and other acute pulmonary complications of crack cocaine inhalation promote transmission. Drug users are more likely than non-drug users to default treatment, to remain infectious for prolonged periods after diagnosis, and to acquire drug-resistant TB (15). We studied smear status at diagnosis to exclude the effect of poor treatment adherence. Our study suggests a dangerous synergy between TB and crack cocaine. Users may experience addiction-related problems that complicate access to healthcare and aggravate transmission, possibly aggravated by a biological driver that may increase susceptibility to infection and progression to infectious disease Infectious disease A pathological condition spread among biological species. Infectious diseases, although varied in their effects, are always associated with viruses, bacteria, fungi, protozoa, multicellular parasites and aberrant proteins known as prions. . Additional studies are needed to investigate the possible biological role of crack cocaine in the development of infectious forms of TB. DOI (Digital Object Identifier) A method of applying a persistent name to documents, publications and other resources on the Internet rather than using a URL, which can change over time. : 10.3201/eid 1409.070654; This study was funded by the Health Protection Agency and the Department of Health for England and Wales England and Wales are both constituent countries of the United Kingdom, that together share a single legal system: English law. Legislatively, England and Wales are treated as a single unit (see State (law)) for the conflict of laws. . References (1.) Story A, Murad S, Verheyen M, Roberts W, Hayward AC. Tuberculosis in London: the importance of homelessness, problem drug use and prison. Thorax thorax, body division found in certain animals. In humans and other mammals it lies between the neck and abdomen and is also called the chest. The skeletal frame of the thorax is formed by the sternum (breastbone) and ribs in front and the dorsal vertebrae in back. . 2007;62:667-71. DOI: 10.1136/thx.2006.065409 (2.) Condon J, Smith N. Prevalence of drug use: key findings from the 2002/2003 British Crime Survey The British Crime Survey or BCS is a systematic victim study, currently carried out by BMRB Limited on behalf of the Home Office. The BCS seeks to measure the amount of crime in England and Wales by asking around 50,000 people aged 16 and over, living in private households, . Home Office Findings, 229. London: Home Office; 2003 [cited 28 Jul 2008]. Available from http:// www.hjomeoffice.gov.uk/rds/pdfs2/r229.pdf (3.) Payne-James JJ, Wall I J, Bailey C. Patterns of illicit drug use of prisoners in police custody in London, UK. J Clin Forensic Med. 2005;12:1968. DOI: 10.1016/j.jcfm.2005.04.005 (4.) Hope VD, Hickman M, Tilling K. Capturing crack cocaine use: estimating the prevalence of crack cocaine use in London using capture-recapture with covariates. Addiction. 2005;100:1701-8. DOI: 10.1111/j.1360-0443.2005.01244.x (5.) Howard AA, Klein RS, Schoenbaum EE, Gourevitch MN. Crack cocaine use and other risk factors for tuberculin positivity in drug users. Clin Infect Dis. 2002;35:1183-90. DOI: 10.1086/343827 (6.) Baldwin GC, Tashkin DP, Buckley DM, Park AN, Dubinett SM, Roth MD. Marijuana and cocaine impair alveolar macrophage function and cytokine production. Am J Respir Crit Care Med. 1997;156:1606-13. (7.) Dannenberg AM Jr. Pathogenesis of pulmonary tuberculosis. Am Rev Respir Dis. 1982;125:25-9. (8.) Mehta PK, Karls RK, White EH, Ades EW, Quinn FD. Entry and intracellular replication of Mycobacterium tuberculosis in cultured human microvascular endothelial cells. Microb Pathog. 2006;41:119-24. Epub 2006 Jul 24. DOI: 10.1016/j.micpath.2006.05.002 (9.) Laposata EA, Mayo GL. A review of pulmonary pathology and mechanisms associated with inhalation of freebase free·base or free-base v. free·based, free·bas·ing, free·bas·es v.tr. 1. To purify (cocaine) by dissolving it in a heated solvent and separating and drying the precipitate. 2. cocaine ("crack"). Am J Forensic Med Pathol. 1993;14:1-9. (10.) Hirche TO, Lambrecht E, Wagner TO. Crack-syndrome: the pulmonary complications of inhaled cocaine. A review a propos a case report [in German]. Pneumologie. 2002;56:684-8. DOI: 10.1055/ s-2002-35552 (11.) Isoniazid isoniazid (ī'sōnī`əzĭd), drug used to treat tuberculosis. Also known as isonicotinic acid hydrazide, isoniazid is the most effective antituberculosis drug currently available. mono-resistant tuberculosis in north London update. CDR (1) See CD-R and extension. (2) (Call Detail Reporting) See call accounting. (3) (Common Data Rate) A standard sampling rate for digital video for 480i and 576i systems. The rate is 13.5 MHz. See ITU-R BT. Weekly. 2006;16:2 [cited 28 Jul 2008]. Available from http:// www.hpa.org.uk/cdr/archives/archive04/news/news1204.htm (12.) Riley LW, Arathoon E, Loverde VD. The epidemiologic patterns of drug resistance in Mycobacterium tuberculosis infections: a community-based study. Am Rev Respir Dis. 1989;139:1282-5. (13.) Roth MD, Whittaker K, Salehi K, Tashkin DE Baldwin GC. Mechanisms for impaired effector effector /ef·fec·tor/ (e-fek´ter) 1. an agent that mediates a specific effect. 2. an organ that produces an effect in response to nerve stimulation. function in alveolar macrophages from marijuana and cocaine smokers. J Neuroimmunol. 2004;147:82-6. DOI: 10.1016/j.jneuroim.2003.10.017 (14.) Leonhardt KK, Gentile F, Gilbert BP, Aiken M. A cluster of tuberculosis among crack house contacts in San Mateo County, California San Mateo County is a county located in the San Francisco Bay Area of the U.S. state of California. It covers most of the San Francisco Peninsula just south of San Francisco, near San Francisco State University, and north of Santa Clara County. . Am J Public Health. 1994;84:1834-6. (15.) Pablos-Mendez A, Knirsch CA, Barr RG, Lerner BH, Frieden TR. Nonadherence in tuberculosis treatment: predictors and consequences in New York City New York City: see New York, city. New York City City (pop., 2000: 8,008,278), southeastern New York, at the mouth of the Hudson River. The largest city in the U.S. . Am J Med. 1997;102:164-70. DOI: 10.1016/ S0002-9343(96)00402-0 Address for correspondence: Alistair Story, Tuberculosis Section, Respiratory Diseases Department, Health Protection Agency, Centre for Infections, 61 Colindale Ave, London NW9 5EQ, UK; email: alistair. story@hpa.org.uk Author affiliations: Health Protection Agency, London, UK (A. Story); Homerton Hospitals National Health Service Foundation Trust, London (G. Bothamley); and University College London “UCL” redirects here. For other uses, see UCL (disambiguation). University College London, commonly known as UCL, is the oldest multi-faculty constituent college of the University of London, one of the two original founding colleges, and the first British Centre for Infectious Disease Epidemiology, London (A. Hayward) Mr Story is a consultant nurse and epidemiologist at the Health Protection Agency Centre for Infections, London. His main area of interest is the control and public health effect of infections among hard-to-reach groups, particularly drug users, prisoners, and the homeless.
Table 1. Univariate analysis of drug-using and non-drug-using patients
with pulmonary TB in London, United Kingdom, 2003-2004 *
Hard-drug user
No known drug (unconfirmed
use, n = 833, crack cocaine
Variable no. (%) user), n = 115,
no. (%)
Gender
Male 445 (54.1) 99 (86.8)
Female 377 (45.9) 15 (13.2)
Ethnicity
White 142 (17.1) 54 (47.0)
Black African 344 (41.5) 25 (21.7)
Black Caribbean 32 (3.9) 15 (13.0)
South Asian 244 (29.4) 17 (14.8)
Other 68 (8.2) 4 (3.5)
Born in the United Kingdom 162 (19.6) 62 (54.9)
Previous TB 78 (9.4) 25 (21.7)
Previous TB past 2 years (relapsed) 36 (4.3) 19 (16.5)
Known HIV+ 95 (11.4) 9 (7.8)
Delay in diagnosis [greater than or
equal to] 3 mo 109 (13.1) 19 (16.5)
Sought treatment at ED 126 (15.1) 32 (27.8)
Cough during initial examination 589 (70.7) 99 (86.1)
Sputum smear positive at diagnosis 302 (36.3) 68 (59.1)
MDR 32 (3.8) 7 (6.1)
Linked to known INH resistance
outbreak 9 (1.1) 10 (8.7)
INH resistance (not outbreak) 54 (6.5) 11 (9.6)
Treated with DOT from start 74 (9.0) 19 (16.5)
Nonadherent to treatment in first 2
mo 125 (15.0) 59 (51.3)
Lost to follow-up 19 (2.3) 12 (10.4)
Homeless 37 (4.4) 22 (19.1)
Mental health problems 28 (3.4) 27 (23.5)
Imprisoned during current episode
of TB 9 (1.1) 22 (19.1)
Hard-drug user
(confirmed
crack cocaine
Variable user), n = 22,
no. (%) p value
Gender <0.0001
Male 12 (54.6)
Female 10 (45.5)
Ethnicity <0.0001
White 5 (22.7)
Black African 5 (22.7)
Black Caribbean 9 (40.9)
South Asian 0
Other 3 (13.6)
Born in the United Kingdom 14 (63.7) <0.0001
Previous TB 5 (22.7) <0.0001
Previous TB past 2 years (relapsed) 4 (18.2) <0.0001
Known HIV+ 3 (13.6) 0.478
Delay in diagnosis [greater than or
equal to] 3 mo 2 (9.1) 0.499
Sought treatment at ED 10 (45.6) <0.0001
Cough during initial examination 19 (86.40) 0.001
Sputum smear positive at diagnosis 19 (86.4) <0.0001
MDR 0 0.333
Linked to known INH resistance
outbreak 11 (50.0) <0.0001
INH resistance (not outbreak) 1 (4.5) 0.783
Treated with DOT from start 6 (27.3) 0.001
Nonadherent to treatment in first 2
mo 15 (68.2) <0.0001
Lost to follow-up 6 (27.3) <0.0001
Homeless 13 (59.1) <0.0001
Mental health problems 9 (40.9) <0.0001
Imprisoned during current episode
of TB 14 (63.6) <0.0001
* TB tuberculosis ED emergency department; MDR, multidrug resistant;
INH, isoniazid; DOT, directly observed therapy.
Table 2. Multivariate analysis of risk factors for smear-positive
disease on diagnosis among drug-using and non-drug-using
patients with pulmonary TB in London, UK, 2003-2004 *
Variable OR 95% CI p value
Not a hard-drug user Baseline
Hard-drug user (not known 1.87 1.19-2.95 0.007
to use crack cocaine)
Crack cocaine user 6.59 1.78-24.31 0.005
Age, y
0-14 0.10 0.08-0.56 0.002
15-29 1.10 0.81-1.48 0.55
30-59 Baseline
[greater than or equal to] 60 0.69 0.45-1.14 0.14
Ethnicity
South Asian Baseline
Black African 1.75 0.96-1.95 0.08
White 1.51 0.99-2.31 0.053
Black Caribbean 2.70 1.34-5.43 0.005
Other ethnicity 1.61 0.91-2.85 0.101
No drug resistance Baseline
INH (not outbreak strain) 1.23 0.72-2.11 0.441
INH (outbreak strain) 0.96 0.37-2.50 0.929
MDR 2.90 1.44-5.78 0.003
Sought treatment at ED 3.33 2.20-4.82 <0.001
* OR, odds ratio; CI, confidence interval; INH, isoniazid resistant;
MDR, multidrug-resistant; ED, emergency department.
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