Drug abuse profile – patient delay,diagnosis delay and drug resistance pattern

Abstract

Socioeconomic problems limit the access of drug users to health-care services. This descriptive cross-sectional study was carried out by making use of the medical records of new case tuberculosis (TB) patients hospitalized at Masih Daneshvari Hospital, the national referral centre in Iran, from 2003 to 2006. Demographic and personal characteristics of the patients and type of disease were collected and categorized. Of the 944 patients with confirmed TB, 143 (15.1%) were drug users, among whom 140 (97.9%) were men with just three women drug users. The mean age of the drug users group was 43.04 ± 13.81 years. The type of drug used was opium in 100 cases (69.9%), heroin in 29 (20.3%), opium and heroin together in four (2.8%) and all three, opium, heroin and crack, in two (1.4%). For 238 high-risk patients, an HIV test was performed and HIV infection was confirmed in 33 cases. Patient delay was longer in drug users (P = 0.000) against other patients, whereas diagnosis delay was shorter (P = 0.007). Drug susceptibility tests were performed for 515 patients with positive cultures. One hundred and thirty-three (14.1%) were found to have ‘any resistance’ to anti-TB drugs, and 10 (1.1%) individuals had multidrug-resistant TB. Twenty-six (19.5%) of the individuals who showed resistance to first-line agents were drug users. There was no significant relation between drug resistance and drug use (P = 0.4). In conclusion, it seems that active case finding for TB and HIV in addict cases must be contained in harm reduction packages. Moreover, the manifestations of the disease should be considered seriously regardless of attributing them to drug use.

Keywords

tuberculosis drug abuse patient delay

INTRODUCTION

Iran, like many other countries, has had high opium addiction rates in the past few decades. According to Razzaghi et al. ¹, 20% of Iranians between the ages of 15 and 60 are involved in drug abuse. The government estimates that 1.8 million individuals or 9–16% of Iranians inject drugs. Nowadays, it is ever more changed into a social and health problem. In addition to the social problems that addiction incurs in the community, high-risk behaviours, homelessness and poor health status among addicts make them prone to many illnesses, particularly to diverse infectious diseases.^2–4

Moreover, the increasing rate of intravenous drug use (IVDU) along with HIV and hepatitis C virus (HCV) infections has made the problem more overwhelming.^1,5,6

The problem exists to different extents in developing and developed countries where most of the population dwell in urban regions, especially in large cities and metropolitan areas. Likewise, infectious diseases, namely tuberculosis (TB), arise more than ever in specific subgroups mainly alongside growth in the urban inhabitant population.²

As TB is historically said to be the disease of homeless people,^7,8 and is much more common in opium addicts,^2,9 there is a delay in detection of this disease in the aforementioned groups.^2,10

This delay includes two components: patient delay: the time elapsed since the initiation of clinical manifestations till referring or presenting to a physician or health-care services; and diagnosis delay: the duration between the first visit to health-care providers till establishing a definitive diagnosis.

Because the period of infectivity (infectiousness and contagiousness) is the major factor in the transmission of infectious diseases,¹¹ this delay is an important issue in contagious diseases such as TB. Accordingly, its importance is reflected by the fact that early diagnosis and complete and effective treatment is the principal strategy in TB control.^2,10 TB incidence and prevalence rates (all cases/100,000 pop/year) were found to be 22 and 28 accordingly in 2006.¹² However, we do not have any records about TB incidence and prevalence rate in drug addicts in Iran.

Therefore, as early diagnosis and drug susceptibility are two major factors in the treatment of TB (especially in high-risk groups), we intend to determine the profiles of hospitalized TB patients who have a history of drug addiction. Our emphasis will be on the diagnosis delay and drug resistance pattern in the aforementioned patients at Masih Daneshvari Hospital in Tehran, Iran.

METHODS

This descriptive cross-sectional study was carried out by making use of the medical records of all consecutive new case TB patients hospitalized at Masih Daneshvari Hospital from March 2003 to October 2006. Demographic and personal characteristics of the patients, including age, sex, educational level, nationality, history of opium use and clinical symptoms, were retrieved from the patients' histories. The exact time of disease manifestations and the time of first presentation to the health care providers were inquired of each patient during admission to the hospital. Types of disease (smear-positive pulmonary TB, smear-negative pulmonary TB and extrapulmonary TB) were collected and categorized according to the evaluations. Also, we considered drug use as opium, heroin or crack use. Current or any history of intravenous drug use was notified as well. Drug addiction was defined as persistent use along with dependency on the material, while temporary drug use or for recreational/casual purposes was not considered as addiction. Conclusive definitive diagnosis is established based on positive smear or culture of sputum, obtained tissue and other specimens OR histopathological features consistent with TB, accompanied with clinical response to anti-TB medications. Drug resistance was considered as resistance to any first-line anti-TB agent (any resistance). Multidrug-resistant TB (MDR-TB) patients who have concomitant resistance to both isoniazid and rifampicin were also identified. Drug susceptibility testing was performed with the proportional method explained in detail elsewhere.¹³

High-risk patients underwent enzyme-linked immunosorbent assay (ELISA) anti-HIV Ab testing for HIV infection, and if resulted positive, the infection was confirmed with Western blot. For statistical analysis, we used SPSS software Version 11.5 (SPSS Inc., Chicago, IL, USA). In this regard, we used chi-square test and if necessary Fisher's exact test for analysis of two groups. For identifying the significance of patient delay and diagnosis delay, we made use of Mann-Whitney U test after testing for variables normal distribution. A P value less than 0.05 is considered as statistically significant.

We analysed the differences between the drug users and non-drug users groups. We also analysed the differences between the two subgroups of opium users (inhalatory form) and intravenous drug users.

Masih Daneshvari Hospital is the national referral centre for TB control and the World Health Organization educational collaborating centre in the Eastern Mediterranean Region (EMR) and possesses a national reference laboratory, required facilities for TB control as well as expert staff in TB management.

The scientific and ethics committee of the National Research Institute of TB and Lung Disease in Iran approved the study protocol.

RESULTS

Of a total of 944 patients with confirmed TB, 143 (15.1%) were drug users, among whom 140 (97.9%) were men and only three women. The mean age of the drug users group was 43.04 ± 13.81 years and most of them (84 people, 58.7%) were in the range of 15–45 years. Forty (27.9%) drug users were illiterate. However, the literacy rate was higher in the drug users group compared to the non-drug users group (P value < 0.05). The type of drug used was opium in 100 cases (69.9%), heroin in 29 (20.3%), opium and heroin together in four (2.8%) and opium, heroin and crack in two (1.4%) people used. The history of close contact to the identified TB patient was positive in 43 (30%) (Table 1).

Table 1

Demographic characteristic of all TB patients, drug users, and its subgroups of opium and intravenous drug use

Type	Total TB patients No. (%)	Drug users No. (%)	P value	Opium (inhalatory form)	IVDU	P value
Sex
Male	469 (49/9)	140 (97.9)	0.000*	100 (99)	35 (100)	0.319
Female	471 (50/1)	3 (2.1)		1 (1)	–
Age (years)
15–45	391 (41.6)	84 (58.7)	0.176	49 (48.5)	31 (88.6)	0.000^†
45–65	241 (25.6)	49 (34.3)		42 (41.6)	4 (11.4)
>65	308 (32.8)	10 (7)		10 (9.9)	–
Education
Illiterate	536 (57)	40 (28)	0.000*	32 (31.7)	3 (8.6)	0.003^†
Diploma and lower	370 (39.4)	98 (68.5)		64 (63.4)	32 (91.4)
Higher education	34 (3.6)	5 (3.5)		5 (5)	–
Nationality
Iranian	722 (76.8)	130 (90.9)	0.000*	95 (94.1)	34 (97.1)	0.14
Others	218 (23.2)	13 (9.1)		6 (5.9)	1 (2.9)
Addiction type
Opium	–	100 (69.9)	–	–	–	–
Heroin		29 (20.3)
Opium + heroin		4 (2.8)
Opium + heroin + crack		2 (1.4)
Positive close contact history	189 (20.1)	43 (30)	0.001*	25 (24.8)	17 (48.6)	0.006
Total	940	143	–	101	35	–

TB = tuberculosis; IVDU = intravenous drug use

*Significant in drug users versus other patients

^†Significant in intravenous drug abuser versus opium addict patients

Of 143 addicted drug users, 127 (88.8%) had sputum smear positive pulmonary tuberculosis (PTBs⁺). Smear-positive PTB was higher in drug users compared with non-drug users (P value = 0.014). However, there was no difference between opium users and intravenous drug users with regard to PTB⁺ (Table 2).

Table 2

Disease characteristic of all TB patients, drug users (and its subgroups of opium inhalatory form and IVDU)

Type	Total TB patients No. (%)	Drug users No. (%)	P value	Opium (inhalatory form)	IVDU	P value
Patient type
PTBs+	763 (81.2)	127 (88.8)	0.036*	93 (92.1)	28 (80)	0.07
PTBs−	90 (9.6)	7 (4.9)		4 (4)	2 (5.7)
EXPT	87 (9.3)	9 (6.3)		4 (4)	5 (14.3)
Drug resistance
Any resistance	133 (14.1)	26 (18.2)	0.133	19 (18.8)	5 (14.3)	0.492
Sensitive	672 (71.5)	108 (75.5)		82 (81.2)	27 (77.1)
Negative culture	135 (14.4)	9 (6.3)		–	3 (8.6)
MDR-TB	10 (1.1)	2 (1.4)	0.672	1 (1)	1 (2.9)	0.398
HIV
Positive	33 (3.5)	30 (21)	0.000*	14 (13.9)	16 (45.7)	0.000^†
Negative	205 (21.8)	61 (42.7)		45 (44.6)	15 (42.9)
Unknown	702 (74.1)	52 (36.4)		42 (41.6)	4 (11.4)
Respiratory symptoms	904 (96.2)	140 (97.9)	0.241	98 (97)	35 (100)	0.319
Constitutional symptoms	878 (93.4)	141 (98.6)	0.007*	99 (980)	35 (100)	0.417
Total	940	143	–	101	–	–

PTB+ = positive-smear pulmonary TB; PTB − = negative-smear pulmonary TB; EXPT = extra-pulmonary TB; MDR = multidrug-resistant tuberculosis; TB = tuberculosis; IVDU = intravenous drug use

*Significant in drug users verus other patients

^†Significant in intravenous drug abuser versus opium addict patients

At admission, 140 had respiratory symptoms (cough, sputum expectoration, dyspnoea, haemoptysis and chest pain), while 141 (98.6%) had constitutional manifestations including fever, perspiration, weight loss and anorexia.

Totally, 31 (21.7%) had a history of or current use of IVDU. For 238 high-risk patients, anti-HIV AB ELISA was performed and consequently 33 were found to have HIV infection that was confirmed via Western blot. Thirty of HIV-positive patients were drug users, among whom 16 (45.7%) cases were intravenous drug users. HIV infection was significantly higher in drug users. Moreover, it was higher in IVDU than in opium users (P value = 0.05).

Of 944 cases, drug susceptibility tests were performed for 515 patients who had positive cultures. One hundred and thirty-three (14.1%) were found to have ‘any resistance’ to anti-TB drugs and 10 (1.1%) had MDR-TB.

Twenty-six (19.5%) individuals who showed resistance to first-line anti-TB agents were drug users. So, drug resistance rate was determined as 18.2% in drug users and MDR-TB is found in two (1.4%). Any drug resistance as well as MDR-TB demonstrated no difference either between drug users and non-drug users or between opium users and IVDUs (P value = 0.05).

Additionally, type of disease and having respiratory symptoms were not different in the two groups. On the contrary, having constitutional manifestations as well as a history of close contact to confirmed TB patients were significantly higher in the drug users group. The mean of patient delay was 55.3 days more in drug users, while diagnosis delay mean in drug users was 29 days less than in other non-drug users (P value = 0.05). Yet, the total delay was not significantly different in the two groups (Table 3).

Table 3

Patient delay, diagnosis delay and total delay in drug users versus non-drug users (other patients)

Type	Mean (ST deviation)	P value
Patient delay
Drug abusers	64 (58.28)	0.000
Other patients	8.69 (46.38)
Diagnosis delay
Drug abusers	100 (116.54)	0.007
Other patients	129.25 (140.6)
Total delay
Drug abusers	117.48 (121.85)	0.06
Other patients	137/9 (142/75)

Total delay = diagnosis delay + patient delay

DISCUSSION

Although the use of drugs in Iran dates back to many centuries ago, its use was mainly confined to inhalatory opium use and for recreational purposes particularly in the elderly. However, in recent decades drug use has dramatically increased and notably its pattern has chiefly altered to use via the intravenous route. Also, the age of the users has declined to the range of 15–60 years.

It is estimated that currently more than 3.3 million opium users as well as 300,000 IVDUs reside in Iran.^1,14–16

Regarding the fact that TB is more prevalent in special subgroups,² and that these populations are prone to other infectious diseases such as HIV or HCV infections, studies that address these issues in this population (e.g. drug users) are of the greatest importance. Unfortunately, a limited number of studies have been undertaken so far with respect to TB profiles in drug users, and due to the different prevalence and pattern of drug use in each region, these studies are supposed to be performed in each country. Recently, a few studies have been carried out in Iran in the drug users population, mostly with an approach to HIV and HCV infections and harm reduction issues.^1,13,14 These people are at increased risk of exposure and of subsequently being affected by TB because of more frequent risk factors among these groups, including high-risk behaviours, poorly ventilated and illuminated residences, malnutrition, homelessness and poverty.^2,7,8

This study on the TB profile of addict patients is carried out in the national referral centre for TB in Tehran, Iran. As anticipated, addict patients were mostly men and the rate of HIV infection was higher in this group compared with non-drug users TB cases. This finding is mainly due to intravenous drug use. This indicated the necessity of paying more attention to this population, who not only are more at risk but also cause dispersed transmission of the infection in the community. On the other hand, most of these patients were aged between 15 and 45, the largest portion of active and functioning individuals in the community. The type of disease was not different between addicts and non-drug user TB patients. However, drug users present with a more deteriorated general condition, and constitutional manifestations are significantly higher in this group. Although drug resistance did not demonstrate any difference between drug users and non-drug users in our study, drug resistance is different in opium users and IVDUs, according to some other studies.^2,17,18

In the study by Story and colleagues in London,² IVDU and the history of being in prison were associated with drug resistance and in both conditions it was attributed to irregular use of anti-TB medications. Also, the mean patient delay was 55.3 days and higher among drug users (P = 0.000). The potential rationale for this observation may be the more frequent rate of homelessness, poverty, poor access to health services and not admitting these patients in many health centres. Moreover, not caring properly for disease manifestations in these patients and also clinical symptoms suppression due to opium use may also play important roles in this way.

On the other hand, in contrast to some other studies in which the diagnosis delay was higher in IVDUs, we observed a shorter diagnosis delay among drug users in our patients. This may be attributed to the fact that addicts will present and seek for health care, when their disease progresses and their general condition profoundly deteriorates. In addition to more developed disease manifestations at the time of presentation, the referral role of this centre in TB diagnosis and management may be another potential cause for more rapid diagnosis. Yet, in developed countries in which there exists a screening system for HIV-positive and IVDU cases, the delay diagnosis is also reported less and this proposes the importance of screening in these high risk groups.¹⁹

In spite of interestingly significant findings in our study, because of the referral role of our Centre, the results for drug users in our study may not precisely correspond to the status of addicts in the population. Also, HIV and HCV testing was not performed for all patients and the history of imprisonment is retrieved from medical records retrospectively.

This study was undertaken in our national TB referral centre which admits TB patients unconditionally. This may cause higher rates of hospitalization of more drug users in our Centre, mostly with more aggravated conditions.

Reportedly TB, AIDS and HCV infections have experienced a drastically increasing rate in some studies in Iran. Therefore, with regard to its importance in national health issues, performing TB/HIV surveys in this population as well as TB evaluations alone merit consideration in harm reduction packages.

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Drug abuse profile – patient delay,diagnosis delay and drug resistance pattern – among addict patients with tuberculosis