Abstract
The real magnitude of antituberculosis (anti-TB) drug resistance in Saudi Arabia is still unknown because the available data are based on retrospective laboratory studies that were limited to hospitals or cities. A representative national survey was therefore conducted to investigate the levels and patterns of anti-TB drug resistance and explore risk factors. Between August 2009 and July 2010, all culture-positive TB patients diagnosed in any of the tuberculosis reference laboratories of the country were enrolled. Isolates obtained from each patient were tested for susceptibility to first-line anti-TB drugs by the automated Bactec MGIT 960 method. Of the 2,235 patients enrolled, 75 cases (3.4%) were lost due to culture contamination and 256 (11.5%) yielded nontuberculous mycobacteria (NTM). Finally, 1,904 patients (85.2% of those enrolled) had available drug susceptibility testing results. Monoresistance to streptomycin (8.1%; 95% confidence interval [CI], 7.2 to 9.1), isoniazid (5.4%; 95% CI, 4.7 to 6.2), rifampin (1%; 95% CI, 0.7 to 1.3) and ethambutol (0.8%; 95% CI, 0.5 to 1.2) were observed. Multidrug-resistant TB (MDR-TB) was found in 1.8% (95% CI, 1.4 to 2.4) and 15.9% (95% CI, 15.4 to 16.5) of new and previously treated TB cases, respectively. A treatment history of active TB, being foreign-born, having pulmonary TB, and living in the Western part of the country were the strongest independent predictors of MDR-TB. Results from the first representative national anti-TB drug resistance survey in Saudi Arabia suggest that the proportion of MDR-TB is relatively low, though there is a higher primary drug resistance. A strengthened continuous surveillance system to monitor trends over time and second-line anti-TB drug resistance as well as implementation of innovative control measures, particularly among immigrants, is warranted.
INTRODUCTION
Tuberculosis (TB) remains a significant global health problem, with nearly 9 million new cases and 1.5 million deaths estimated annually (1, 2). One of the most dangerous forms of TB is multidrug-resistant TB (MDR-TB), defined as resistance to, at least, isoniazid and rifampin, the two most potent first-line anti-TB drugs. In 2010, there were an estimated 650,000 prevalent cases of MDR-TB worldwide, and at least 150,000 deaths were due to MDR-TB (2, 3). In the same year, 3.4% of all newly diagnosed and 19.8% of all previously treated TB patients were estimated to have MDR-TB (4).
In Saudi Arabia, the true burden of drug-resistant TB is not known, as the country has never conducted a representative national survey to measure levels and patterns of anti-TB drug resistance. World Health Organization (WHO) estimates, which are based on modeling work, suggest that 1.2% (range, 0.7 to 1.6) and 9.0% (range, 5.6 to 12.4) of new and previously treated cases, respectively, are MDR-TB (2). The few small-scale studies conducted in the country reported proportions of resistance to any first-line drugs ranging between 14% and 20% and of MDR-TB ranging between 1% and 44% (5–11). These results should be treated with caution, as these studies were not representative of the country-wide situation, and most were retrospective analyses of laboratory results gathered from hospitals (e.g., armed forces, national guard, and security forces) that are dedicated to specific categories of patients.
The composition of the population of Saudi Arabia is unique for two reasons: nearly one-third of its 27 million inhabitants are immigrant workers, and up to 10 million foreigners visit the country every year for Islamic rituals (hajj and omra) (12). The epidemiology of TB is clearly influenced by immigration and mass gatherings, and these elements should be considered when a representative national survey is being designed (13–16). In Saudi Arabia, all persons suspected of having TB, whether citizens or foreign-born, are screened mainly in nine TB referral laboratories located around the country. These are the major laboratories that diagnose TB in the country and act under the coordination of the National TB Control Program (NTCP). A few referral hospitals also diagnose and treat TB cases in smaller numbers, but they report all the cases to NTCP. The present study depended completely on NTCP-coordinated laboratories and tried to collect all available positive cultures, hence covering the maximum of the reported culture-positive cases.
Our study aimed to investigate levels and patterns of resistance to first-line anti-TB drugs among new and previously treated cases identified in the country following international guidelines and to explore risk factors for the development of multidrug resistance (17).
MATERIALS AND METHODS
Study population.
This study was reviewed and approved by the Research Ethics Committee of King Faisal Specialist Hospital and Research Centre. From August 2009 to July 2010, all patients diagnosed with culture-positive TB in any of the nine TB reference laboratories serving the 13 provinces of Saudi Arabia were eligible for enrolment in the study. Both patients with pulmonary and extrapulmonary disease were enrolled. New patients were defined as those without a history of treatment with first-line anti-TB drugs (isoniazid, rifampin, ethambutol, and streptomycin) or those treated for <1 month; previously treated TB cases were those who had received first-line anti-TB treatment for >1 month (17). A standard data collection questionnaire was used to gather relevant epidemiological and clinical information from each patient. The following variables were recorded: sex, age, place of residence, nationality, treatment history (new/previously treated case), and HIV status. Medical records and the electronic TB information system maintained by the Ministry of Health were reviewed to confirm the reliability of the information collected through the questionnaire (15). All the data collected for the study were anonymous, and no patient identifiers were used throughout data collection and analysis period.
Laboratory methods.
Isolation and identification of mycobacterium isolates were performed on solid Lowenstein-Jensen (LJ) medium in any of the nine TB reference laboratories accredited by the Ministry of Health. All isolates were then sent to the Mycobacteriology Research Section at King Faisal Specialist Hospital and Research Centre, which serves as one of the national TB reference laboratories. Isolates were subcultured into fresh LJ slants and incubated at 37°C. The media were observed on days 3 and 7 to detect contamination and/or growth of nontuberculous mycobacteria (NTM) and subsequently every week to observe growth and colony morphology. Isolates were identified by using the line probe assay (Genotype MTBC; Hain Life Science, Nehren, Germany) according to the manufacturer's instructions. Susceptibility testing was performed on all isolates with an automated Bactec MGIT 960 culture system using a Bactec MGIT SIRE kit from Becton, Dickinson (Sparks, MD). The following drug concentrations were tested: 1 μg/ml for streptomycin, 0.1 μg/ml for isoniazid, 1 μg/ml for rifampin, and 5 μg/ml for ethambutol. Strict quality control testing was performed internally with ATCC strain 27294 and interlaboratory clinical isolates. In addition, the laboratory has on a regular enrollment in an external proficiency survey with the Supranational TB Reference Laboratory (WHO) in Cairo, Egypt, and the College of American Pathologists in Chicago, IL.
Data analysis.
Data were entered in duplicate into Microsoft Access software (Microsoft, Redmond, WA) for validation, and discrepancies were checked against raw data. Data analysis was conducted using the software packages SPSS version 19.0 (IBM Corporation, NY) and STATA, release 12.0 (Stata Corporation, TX). Pearson's χ2 statistics or Fisher's two-tailed test was used to compare categorical variables. All variables were studied in a univariate analysis; those with P values of <0.05 were included in a multivariate logistic regression analysis. Confounding effects were checked using backward regression analysis (a cutoff P value of <0.05 was used to exclude variables from the model). In all analyses, confidence intervals and P values were corrected for definite population and clustering effect.
RESULTS
Study population.
During the survey intake period 2,235 patients were enrolled from all 13 provinces of the country. Of them, 75 (3.4%) were excluded because the isolates were lost due to culture contamination, and 256 (11.5%) were infected with NTM, leaving a total of 1,904 patients (85.2% of those enrolled) with available drug susceptibility testing results that could be included in the analysis. The proportion of male patients was higher overall (male/female ratio, 1.7) and ranged from 1.1 to 3.5 in all regions except in Medina province (in the west), where the male/female ratio was 0.8. The age groups of 16 to 29 (34.8%) and 30 to 44 (32.8%) years old were the most affected by TB. Half of the patients were born in Saudi Arabia (50.7%, 966/1,904), 23.3% (443/1,904) had smear-negative culture-positive TB, and the vast majority had no history of treatment for TB (84.5%, 1,609/1,904). Most patients in the study had pulmonary TB (79.3%, 1,509/1,904). Extrapulmonary TB was observed among 381 (20%) patients. The lymph nodes were the major site of infection (56.2% cases). Data on HIV status were available for only 46.3% (881/1,904) of all patients, and 17 (1.9%) of them were found to be HIV positive. Only 3 (17.6%) patients among 17 HIV-positive cases were infected with extrapulmonary TB (lymph node only). Data on the history of TB treatment and additional characteristics of the study population are shown in Table 1.
Table 1.
Demographical summary of the study subjectsa
| Characteristic | Central |
East |
North |
South |
West |
Total |
P | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. | % | No. | % | No. | % | No. | % | No. | % | No. | % | ||
| Total | 577 | 30.3 | 355 | 18.6 | 22 | 1.2 | 241 | 12.7 | 709 | 37.3 | 1,904 | 100.0 | |
| Sex | 0.001 | ||||||||||||
| Male | 374 | 64.8 | 239 | 67.3 | 13 | 59.1 | 158 | 65.6 | 411 | 58.0 | 1,195 | 62.8 | |
| Female | 203 | 35.2 | 114 | 32.1 | 9 | 40.9 | 83 | 34.4 | 293 | 41.3 | 702 | 36.9 | |
| Not reported | 2 | 0.6 | 5 | 0.7 | 7 | 0.4 | |||||||
| Age (yrs) | <0.001 | ||||||||||||
| Up to 15 | 10 | 1.7 | 13 | 3.7 | 1 | 4.6 | 11 | 4.6 | 47 | 6.6 | 82 | 4.3 | |
| 16–29 | 180 | 31.2 | 120 | 33.8 | 4 | 18.2 | 74 | 30.7 | 285 | 40.2 | 663 | 34.8 | |
| 30–44 | 202 | 35.0 | 136 | 38.3 | 10 | 45.5 | 73 | 30.3 | 204 | 28.8 | 625 | 32.8 | |
| 45–59 | 110 | 19.1 | 67 | 18.9 | 3 | 13.6 | 39 | 16.2 | 102 | 14.4 | 321 | 16.9 | |
| Over 60 | 68 | 11.8 | 19 | 5.4 | 4 | 18.2 | 41 | 17.0 | 66 | 9.3 | 198 | 10.4 | |
| Not reported | 7 | 1.2 | 3 | 1.2 | 5 | 0.7 | 15 | 0.5 | |||||
| Nationality | 0.058 | ||||||||||||
| Saudi Arabia | 288 | 49.9 | 166 | 46.8 | 12 | 54.6 | 134 | 55.6 | 366 | 51.6 | 966 | 50.7 | |
| Foreign | 287 | 49.7 | 188 | 53.0 | 10 | 45.5 | 107 | 44.4 | 338 | 47.7 | 930 | 48.8 | |
| Not reported | 2 | 0.4 | 1 | 0.3 | 5 | 0.7 | 8 | 0.4 | |||||
| Smear results | <0.001 | ||||||||||||
| Positive | 386 | 66.9 | 268 | 75.5 | 20 | 90.9 | 208 | 86.3 | 579 | 81.7 | 1,461 | 76.7 | |
| Negative | 191 | 33.1 | 87 | 24.5 | 2 | 9.1 | 33 | 13.7 | 130 | 18.3 | 443 | 23.3 | |
| Treatment history | 0.001 | ||||||||||||
| New | 477 | 82.7 | 323 | 91.0 | 14 | 63.6 | 192 | 79.7 | 603 | 85.0 | 1,609 | 84.5 | |
| Previously treated | 100 | 17.3 | 32 | 9.0 | 8 | 36.4 | 49 | 20.3 | 106 | 15.0 | 295 | 15.5 | |
| Site of disease | <0.001 | ||||||||||||
| Pulmonary | 492 | 85.3 | 230 | 64.8 | 21 | 95.5 | 210 | 87.1 | 556 | 78.4 | 1,509 | 79.3 | |
| Extrapulmonary | 81 | 14.0 | 125 | 35.2 | 1 | 4.6 | 31 | 12.9 | 143 | 59.3 | 381 | 20.0 | |
| Not reported | 4 | 0.7 | 10 | 4.1 | 14 | 0.7 | |||||||
| HIV status | <0.001 | ||||||||||||
| Positive | 3 | 0.5 | 4 | 1.7 | 10 | 1.4 | 17 | 0.9 | |||||
| Negative | 167 | 28.9 | 153 | 43.1 | 9 | 40.9 | 106 | 44.0 | 429 | 60.5 | 864 | 45.4 | |
| Unknown | 407 | 70.5 | 202 | 56.9 | 13 | 59.1 | 131 | 54.4 | 270 | 38.1 | 1,023 | 53.7 | |
Geographical location of TB reference laboratories: central, Riyadh; east, Dammam; north, Hail; south, al-Baha, Aseer, and Jizan; west, Jeddah, Taif, and Medina.
Drug resistance pattern.
Of the 1,609 isolates from new cases of TB, 16.4% (95% CI, 15.0 to 17.8) were resistant to at least one first-line drug and 1.8% (95% CI, 1.4 to 2.4) were MDR. Resistance to only one of the four first-line drugs (defined as mono-drug resistance) was found in 12.0% (95% CI, 10.8 to 13.3) of all new cases, and resistance to more than one of the first-line drugs but not MDR (defined as poly-drug resistance) was detected in 2.6% (95% CI, 2.0 to 3.2) of all new cases. Resistance to isoniazid, rifampin, ethambutol, and streptomycin in new cases is shown in Table 2.
Table 2.
Resistance to first-line anti-TB drugs
| Type of resistancea | % of patients with resistance (95% CI)b |
||
|---|---|---|---|
| New (n = 1,609) | Previously treated (n = 295) | All (n = 1,904) | |
| Any drug resistance | 16.4 (15.0–17.8) | 63.4 (62.8–64.1) | 23.6 (22.2–25.1) |
| H | 7.5 (6.6–8.6) | 40.0 (39.3–40.7) | 12.6 (11.5–13.7) |
| R | 2.6 (2.0–3.2) | 20.3 (18.8–20.9) | 5.3 (4.6–6.1) |
| E | 3.3 (2.7–4.1) | 19.7 (19.1–20.3) | 5.8 (5.1–6.7) |
| S | 10.5 (9.4–11.8) | 39.3 (38.6–40.1) | 15.0 (13.8–16.2) |
| Mono-drug resistance | 12.0 (10.8–13.3) | 32.9 (32.2–33.6) | 15.2 (14.0–16.5) |
| H | 4.0 (3.3–4.8) | 13.2 (12.7–13.7) | 5.4 (4.7–6.2) |
| R | 0.6 (0.4–1.0) | 2.7 (2.5–2.9) | 1.0 (0.7–1.3) |
| E | 0.7 (0.4–1.1) | 1.4 (1.2–1.5) | 0.8 (0.5–1.2) |
| S | 6.7 (5.8–7.8) | 15.6 (15.1–16.1) | 8.1 (7.2–9.1) |
| MDR-TB | 1.8 (1.4–2.4) | 15.9 (15.4–16.5) | 4.0 (3.4–4.7) |
| Poly-drug resistance | 2.6 (2.0–3.2) | 14.6 (14.1–15.1) | 4.4 (3.8–5.2) |
H, isoniazid; R, rifampin; E, ethambutol; S, streptomycin.
“New” refers to newly diagnosed TB patients; “previously treated” refers to patients who had received treatment for >1 month prior to the study.
Of the 295 isolates from previously treated TB cases, 63.4% (95% CI, 62.8 to 64.1) were resistant to at least one first-line drug and 15.9% (95% CI, 15.4 to 16.5) had MDR-TB. Mono-drug and poly-drug resistance rates were 32.9% (95% CI, 32.2 to 33.6) and 14.6% (95% CI, 14.1 to 15.1), respectively. Resistance to isoniazid, rifampin, ethambutol, and streptomycin in previously treated cases is shown in Table 2.
Geographical distribution of MDR-TB.
Overall proportions of MDR-TB varied within the country. The highest proportion was detected in northern provinces (9.1%; 95% CI, 2.0 to 32.6), but only a few patients (22 cases) were enrolled from this area. The second highest proportion was found in southern provinces (5.4%; 95% CI, 3.2 to 9.0), followed by western provinces (4.9%; 95% CI, 3.7 to 6.6) and central provinces (3.8%; 95% CI, 2.6 to 5.6). The lowest proportion of MDR-TB was reported from the eastern province (1.1%; 95% CI, 0.4 to 2.9). Table 3 shows the distribution of MDR-TB in the five geographical areas of the country for patients with a history of treatment.
Table 3.
Geographic distribution of MDR-TB in Saudi Arabia during 2009–2010
| Geographical area | Newa |
Previously treated |
All |
|||
|---|---|---|---|---|---|---|
| No. tested | % with MDR-TB (95% CI) | No. tested | % with MDR-TB (95% CI) | No. tested | % with MDR-TB (95% CI) | |
| Central | 477 | 1.7 (0.9–3.2) | 100 | 14.0 (9.2–20.7) | 577 | 3.8 (2.6–5.6) |
| East | 323 | 0.93 (0.3–2.7) | 32 | 3.1 (0.4–19.1) | 355 | 1.1 (0.4–2.9) |
| North | 14 | 0 | 8 | 25.0 (4.2–71.9) | 22 | 9.1 (2.0–32.6) |
| South | 192 | 0 | 49 | 26.5 (16.5–39.7) | 241 | 5.4 (3.2–9.0) |
| West | 603 | 2.99 (2.0–4.5) | 106 | 16.0 (11.1–22.6) | 709 | 4.9 (3·7–6.6) |
Newly diagnosed cases.
Risk factors for MDR-TB.
As expected, history of anti-TB treatment is the strongest independent predictor of MDR-TB (odds ratio [OR], 9.3; 95% CI, 6.5 to 13.3; P < 0.001). The multivariate analysis also shows that being foreign-born strongly increases the risk of MDR-TB (OR, 1.6; 95% CI, 1.1 to 2.3; P = 0.016). Patients living in the western provinces have a significantly higher risk of MDR-TB (OR, 1.6; 95% CI, 1.0 to 2.5, P = 0.041) and those living in the eastern province have a significantly lower risk (OR, 0.4; 95% CI, 0.2 to 0.9; P = 0.035) than those in the rest of the country. Finally, patients with extrapulmonary TB have a significantly lower risk of MDR-TB than those with pulmonary TB (OR, 0.5; 95% CI, 0.3 to 0.9; P = 0.015). Associations between MDR-TB and sex, age, smear results, and HIV were not found to be statistically significant (Table 4).
Table 4.
Risk factors for MDR-TB in Saudi Arabia among new and previously treated cases
| Factor | No. tested | % with MDR-TB | Univariate analysis |
Multivariate analysis |
||||
|---|---|---|---|---|---|---|---|---|
| OR | 95% CI | P | OR | 95% CI | P | |||
| Sex | ||||||||
| Male | 1,195 | 41.0 | ||||||
| Female | 702 | 37.0 | 0.9 | 0.6–1.3 | 0.576 | |||
| Not reported | 7 | 14.3 | 3.9 | 0.8–20.0 | 0.103 | |||
| Age (yrs) | ||||||||
| Up to 15 | 82 | 2.4 | ||||||
| 16–29 | 663 | 3.0 | 1.2 | 0.4–3.8 | 0.704 | 1.2 | 0.4–4.0 | 0.738 |
| 30–44 | 625 | 5.4 | 2.3 | 0.8–7.0 | 0.140 | 2.0 | 0.6–6.4 | 0.239 |
| 45–59 | 321 | 4.4 | 1.8 | 0.6–5.8 | 0.306 | 1.7 | 0.5–5.8 | 0.391 |
| Over 60 | 198 | 2.0 | 0.8 | 0.2–3.1 | 0.774 | 0.8 | 0.2–3.5 | 0.822 |
| Not reported | 15 | 13.3 | 6.2 | 1.3–29.5 | 0.023 | 2.7 | 0.5–13.3 | 0.226 |
| Nationality | ||||||||
| Saudi Arabia | 966 | 3.0 | ||||||
| Foreign | 930 | 5.0 | 1.7 | 1.2–2.4 | 0.005 | 1.6 | 1.1–2.3 | 0.016 |
| Not reported | 8 | 12.5 | 4.6 | 0.9–23.6 | 0.066 | 4.3 | 0.7–27.9 | 0.129 |
| Geographical area | ||||||||
| Central | 577 | 3.8 | ||||||
| East | 355 | 1.1 | 0.3 | 0.1–0.7 | 0.003 | 0.4 | 0.2–0.9 | 0.035 |
| North | 22 | 9.1 | 2.5 | 0.8–8.1 | 0.118 | 1.5 | 0.5–4.9 | 0.486 |
| South | 241 | 5.4 | 1.4 | 0.8–2.5 | 0.186 | 1.4 | 0.8–2.4 | 0.271 |
| West | 709 | 4.9 | 1.3 | 0.9–2.0 | 0.205 | 1.6 | 1.0–2.5 | 0.041 |
| Smear results | ||||||||
| Positive | 1,461 | 4.0 | ||||||
| Negative | 443 | 3.8 | 0.9 | 0.6–1.4 | 0.805 | |||
| Treatment history | ||||||||
| New | 1,609 | 1.8 | ||||||
| Previously treated | 295 | 15.9 | 10.3 | 7.1–14.9 | 0.000 | 9.3 | 6.5–13.3 | <0.001 |
| Site of disease | ||||||||
| Pulmonary | 1,509 | 4.5 | ||||||
| Extrapulmonary | 381 | 2.1 | 0.5 | 0.3–0.8 | 0.007 | 0.5 | 0.3–0.9 | 0.015 |
| Not reported | 14 | 0.0 | ||||||
| HIV status | ||||||||
| Positive | 17 | 5.9 | ||||||
| Negative | 864 | 4.5 | 0.8 | 0.2–3.6 | 0.727 | |||
| Unknown | 1,023 | 3.5 | 0.6 | 0.1–2.8 | 0.501 | |||
DISCUSSION
This study presents the findings of the first representative national survey conducted in Saudi Arabia following international standards to measure the burden of drug-resistant TB. Our results cannot be compared with those obtained in lower-scale studies performed in the past in the country, as those surveys were not designed to gather population-based representative information and were conducted in selected referral hospitals that usually handle the most complicated cases of TB (5–9, 11). When our findings are compared with the results of similar surveys conducted in the context of the WHO global project on anti-TB drug resistance surveillance, it is evident that drug resistance is not a major problem in Saudi Arabia, where the proportion of MDR-TB among newly diagnosed cases is among the lowest reported globally and in the WHO eastern Mediterranean region.
As this was the first representative survey conducted in the country, we are not in a position to evaluate time trends in drug resistance, but previous reports from the western and central provinces suggest that resistance to anti-TB drugs may be increasing (10, 11). This finding should be confirmed by repeating a national survey in a few years' time or, ideally, by establishing a continuous surveillance system based on routine drug susceptibility testing of all bacteriologically confirmed TB cases. Continuous surveillance is indeed the best approach to monitor time trends and is recommended by the WHO (18).
An interesting finding of our study is that, even if the proportion of MDR-TB in the country is low, there are significant variations in rates of MDR-TB between provinces. Northern provinces appear to have higher proportions of MDR-TB but the difference with the rest of the country is not statistically significant because of the very limited number of patients tested in those areas. The fact that TB patients living in the Western provinces and in the Eastern province have, respectively, significantly higher and lower risks of MDR-TB than those in the rest of the country, which has instead important implications for TB and MDR-TB control. A recent study showed that western provinces, and in particular the Makkah province, have the highest TB incidence in the country (26/100,000 in Makkah) (15). This is explained by the fact that Makkah is the holy place for Muslims and is visited annually by millions of pilgrims from high countries where TB is highly endemic, including Pakistan, Bangladesh, India, Somalia, Sudan, Ethiopia, and Eritrea. Hajj has been shown to represent a formidable opportunity for transmission of infectious diseases, including TB, which is one of the main causes of lung disease contracted during the event (13, 14, 16).
A high degree of heterogeneity in the prevalence of drug resistance has been documented in several countries, including those with larger burden of drug resistance, confirming once again the importance of not relying on national-level estimates but establishing a continuous surveillance system to capture local variations (4, 19).
The strong association documented between MDR-TB and previous treatment with anti-TB drugs is not surprising and has already been described thoroughly in the medical literature (20–22). Interestingly, patients with extrapulmonary TB were also enrolled in our survey. This group of patients is usually excluded from these studies due to the challenges of diagnosing extrapulmonary TB (17). Patients with extrapulmonary disease appear to have a significant lower proportion of MDR-TB compared to those with pulmonary disease. This finding has not been widely documented in the literature and should be further investigated. On the other hand, current findings showed no prevalence of gender or nationality among extrapulmonary TB cases, while previous single-institution-based studies showed that extrapulmonary diseases account for 30% of all newly diagnosed TB cases and predominated among female and foreign-born patients (23, 24).
In Saudi Arabia, more than nine million people—one third of the total population—are immigrant workers (12). The incidence of TB in this population group is known to be two times higher than that among citizens and is increasing (15). Our study suggests that the foreign-born have not only a significantly higher incidence of TB but also a significantly higher proportion of MDR-TB than the rest of the patients. This is not surprising considering the countries of origin. Innovative public health measures should be investigated to improve prevention and control of TB and MDR-TB among immigrant workers. This is of paramount important if Saudi Arabia wants to move toward elimination of TB.
The incidence of TB in people living with HIV in Saudi Arabia is 30 times higher than that in the general population, but the number of people with HIV infection is relatively small, with just 217 people having been identified as being infected with HIV in the decade 1997-2007 (25). In our survey, there were only 17 patients with TB-HIV coinfection (<1% of those enrolled), and the majority of those enrolled had unknown HIV status. The lack of association between MDR-TB and HIV found in our study is therefore not surprising, but this finding should not be considered conclusive because of the large proportion of patients with unknown HIV status.
However, one limitation of this study is that testing for susceptibility to second-line anti-TB drugs was not performed. Extensively drug resistant TB (XDR-TB), which is defined as MDR-TB that also has resistance to at least a fluoroquinolone and one second-line injectable agent (amikacin, kanamycin, and/or capreomycin), has not been detected yet in Saudi Arabia, but this is likely due to the fact that susceptibility testing to second-line anti-TB drugs is not routinely performed in this country.
Our study shows that Saudi Arabia has a relatively low prevalence of MDR-TB; however, MDR-TB is not uniformly distributed throughout the country but rather is more concentrated in the western provinces and in the large population of immigrant workers. This analysis calls for a strengthened surveillance system to monitor time trends in drug resistance and assess levels and patterns of resistance to second-line anti-TB drugs. In addition, in order to move toward TB elimination, innovative measures should be introduced in Saudi Arabia to tackle the problem of MDR-TB in specific geographic areas and among immigrant workers, a group at high risk for TB and MDR-TB.
ACKNOWLEDGMENTS
This study was supported by grant AT-110/26 from the King Abdulla City for Science and Technology, Riyadh, Saudi Arabia.
M.Z. and M.C.R. are staff members of the World Health Organization. The authors alone are responsible for the views expressed in this publication, which do not necessarily represent the decisions or policies of the World Health Organization.
Footnotes
Published ahead of print 4 March 2013
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