SUMMARY All published material on the prevalence of drug-resistant tuberculosis within Saudi Arabia over the period 1979–98 was reviewed. The prevalence of single-drug-resistant tuberculosis ranged from 3.4% to 41% for isoniazid, 0% to 23.4% for rifampicin, 0.7% to 22.7% for streptomycin and 0% to 6.9% for ethambutol. The prevalence of multidrug-resistant tuberculosis (defined by WHO as resistance to two or more first-line antituberculosis drugs) ranged from 1.5% to 44% in different regions. No strong conclusions could be drawn owing to variations in the populations studied, geographical origins, site of Mycobacterium tuberculosis isolation (pulmonary or extrapulmonary) and drug sensitivity testing. However, the need to develop a standardized national policy for surveillance of drug-resistant tuberculosis in Saudi Arabia is clear.

After years of decline, tuberculosis (TB) has re-emerged as a serious public health problem worldwide. In 1993 the World Health Organization (WHO) declared it a global emergency: according to a recent WHO report, there were 7.96 million new cases in 1997 with 2 million deaths [1]. Factors contributing to the resurgence of TB include the human immunodeficiency virus epidemic, immigration of persons from countries with a high incidence of TB, and political turmoil in some developing countries, which has hindered efforts to control the disease.

The re-emergence of TB is a public health concern, especially with increased drug resistance among Mycobacterium tuberculosis strains, which have acquired varying degrees of resistance to first-line antituberculosis drugs. It has been suggested that the underlying causes of single-drug-resistant TB (SDR-TB) and/or multidrug-resistant TB (MDR-TB) may be incorrect treatment, poor compliance with treatment regimens, shortage of antituberculosis drugs due to financial constraints in some developing countries, and deficient or deteriorating TB control programmes, resulting in inadequate administration of effective chemotherapy [2,3]. Previous reports indicate that SDR-TB and MDR-TB are on the increase in both industrialized and developing countries [4,5].

A recent WHO report presented global data on the prevalence of drug-resistant TB for the period 1996–99 [6] (see Table 1). The prevalence of SDR-TB ranged from 2.9% in New Caledonia to 40.8% in Estonia. MDR-TB prevalence ranged from 0% in Finland and New Caledonia to 18.1% in Estonia. Eight countries showed a prevalence of MDR TB greater than 5%. Of the countries that provided two or more data points, Germany (7.7% versus 10.2%) and New Zealand (4.8% versus 12.0%) reported statistically significant increases (P < 0.001) in the prevalence of any drug-resistant TB in the most recent year for which surveillance data were available, compared with the previous year. The Netherlands, on the other hand, reported a significant downward trend (14.1% versus 11.0%, P = 0.02).

The prevalences of SDR-TB and MDR-TB in Saudi Arabia are largely unknown, as only limited-scale studies with variable drug resistance methods were used. In addition, the WHO report on antituberculosis drug resistance did not include data from Saudi Arabia [6]. The objective of this study was to review all published material on the prevalence of SDR-TB and MDR-TB for different regions of Saudi Arabia, to determine the status of antituberculosis drug resistance in the country. Possible reasons for the current status of drug resistance in Saudi Arabia are also discussed.

A MEDLINE search of the world literature from 1966 to September 2001 was performed using ‘tuberculosis’ and ‘Saudi Arabia’ as key words. Any surveys of antimicrobial susceptibility testing of M. tuberculosis isolates performed on isolates from Saudi Arabia were identified. Advice was sought from the Ministry of Health in Riyadh, who is responsible for collecting data on the incidence of TB and drug-resistant status.

For single drugs, the percentage of isolates that were resistant to the drug were recorded. Multidrug resistances reported here were for isolates that were resistant to two or more first-line antituberculosis drugs, according to WHO guidelines [7]. Where particular data were not reported, this was recorded as such. All isolates reported here represent one patient.

Analysis of reports from different areas of Saudi Arabia indicate that the percentage of isolates resistant to isoniazid, as a single drug, were 3.4%–19.4% in Riyadh (located in the central province of Saudi Arabia), 10.3%–28.7% in Jeddah (located in the western province of Saudi Arabia), 6% in Dammam (located in the eastern province of Saudi Arabia), 41% in Gizan (located in the southern province of Saudi Arabia) and 6.5% in Taif (located in the southwest of Saudi Arabia). Resistances to rifampicin, as a single drug, were 0%–9.7%, 5.1%–23.4%, 0.2%, 20% and 15.3% for Riyadh, Jeddah, Dammam, Gizan and Taif respectively. Resistances to streptomycin, as a single drug, were 0.75%–12.5%, 7.7%–22.7%, 0.7%, 26% and 15.9% for Riyadh, Jeddah, Dammam, Gizan and Taif respectively. Resistances to ethambutol, as a single drug, were 2.0%–2.4%, 1.3%–6.9%, 3.9% and 4% for Riyadh, Jeddah, Gizan and Taif respectively. However, 0% resistance to ethambutol was reported from the Dammam area [8] (Table 2). Within SDR-TB, resistance to isoniazid (3.4%–41.0%) was the most common, followed by resistance to rifampicin (0%–23.4%), then streptomycin (0.7%–22.7%) and finally ethambutol (0%–6.9%).

For MDR-TB, reported resistances were 1.5%–11.8%, 11.5%–25.7%, 10.5%, 44% and 15.3% for Riyadh, Jeddah, Dammam, Gizan and Taif respectively (Table 2). The majority of reports found isoniazid and rifampicin to be the most resistant combination, followed by the combination isoniazid, rifampicin and streptomycin [9].

Saudi Arabia, with an area of 865 000 square miles, occupies the bulk of the Arabian peninsula. It is roughly one-third of the size of the United States of America, and the size of western Europe. It is also one of the richest countries in the world, with a comprehensive health care system, which currently has 306 state-run hospitals and 1700 state-run primary health care centres scattered throughout the country.

This review has achieved comprehensive coverage of all possible sources of information about SDR-TB and MDR-TB in Saudi Arabia, from the Internet and other literature searches and from the Ministry of Health (who had no data to add to that published in the literature).

Reports on antituberculosis drug resistance from different regions of Saudi Arabia give a contradictory picture of the status of drug-resistant TB in the country. Reports from Jeddah showed a steady increase in the prevalence of MDR-TB, which increased almost threefold during the period 1991–98 [19]. Suggestions for the cause of the high incidence of drug resistance around Jeddah include exposure of the local population to expatriate workers, illegal immigrants and pilgrims travelling to Mecca [18,20]. Each year around two million pilgrims from all parts of the world pass through Jeddah on their way to Mecca to perform Hajj; most are from poor countries with a high prevalence of infectious diseases such as TB. A recent report has shown that TB was the most common cause of pneumonia requiring hospitalization among the pilgrims in Mecca [21]. Resistance to isoniazid, as a single drug, was the most common, followed by resistance to rifampicin. Similar patterns of high resistance to isoniazid were seen throughout Saudi Arabia (Table 2) [9,22]; this could be a result of non-compliance with treatment regimens or misuse of the drug for chemoprophylaxis [23].

In Riyadh, the prevalence of MDR-TB ranged from 1.5% to 11.8% over the period 1979–97 (Table 2). In one of these studies, conducted at the Riyadh Armed Forces Hospital over the period 1987–97 [15], the authors reported a very low MDR-TB rate of 1.5%. They attributed this to the fact that their study sample consisted mainly of natives, and suggested that the source of highly resistant tubercle bacilli, seen in previous studies from Saudi Arabia, could be expatriates, especially those from the Indian subcontinent. This conclusion was substantiated by two reports from the Riyadh area, which covered natives and the expatriate population and reported relatively high MDR-TB rates of 10.6% and 11.8% [11,14].

There was one report from Taif [13] that showed a high rate of MDR-TB (15.3%) compared with rates in other parts of the country. This high rate in Taif was attributed to possible non-compliance with antituberculosis treatment. This was later confirmed by Al-Hajjaj and Al-Khatim (2000) [23], who investigated the problem of non-compliance thoroughly. They concluded that non-compliance with antituberculosis treatment, despite a retrieval system in operation, was the major cause of the high MDR-TB rate, and called for urgent implementation of a DOTS (directly observed treatment, short course) system in Saudi Arabia.

In Dammam, there was one report concerning MDR-TB [8], which covered the period 1993–96. The prevalence of MDR-TB reported from this area was 10.5%, which is comparable to rates of MDR-TB reported from other parts of Saudi Arabia.

In Gizan, the MDR-TB rate was extremely high (44%) [12] compared with MDR-TB rates reported from other regions of the country [24]. The investigators attributed this to the close proximity of Gizan to the Republic of Yemen, which has been reported to have one of the highest rates of active TB of all Arab countries, and to the movement of labourers across the border, who bring MDR-TB with them [25].

For SDR-TB, the prevalence in Saudi Arabia for the period 1979–98 ranged from 0% to 41% and the highest resistance reported for a single drug was for isoniazid. In comparison, the prevalence of SDR-TB globally, reported recently by WHO [6], ranged from 4.6% to 18.8% (South America), 4.2% to 40.8% (Europe), 8.3% to 20.6% (North America), 15.9% to 27.7% (Africa), 19.2% (the Middle East), 10.5% to 12% [Oceania (Australia and New Zealand)], and 5.1% to 39.4% (Asia). The highest resistance reported for a single drug was for isoniazid [6]. This may be due to the liberal use of this drug for chemoprophylaxis.

For MDR-TB, the prevalence in Saudi Arabia for the period 1979–98 ranged from 1.5% to 44% and the highest resistance was for the drug combination of isoniazid and rifampicin. The WHO report on anti-tuberculosis treatment [6] presented MDR-TB rates that ranged from 0.2% to 1.1% (South America), 0% to 18.1% (Europe), 0.9% to 7.3% (North America), 1.5% to 3.5% (Africa), 8.1% (the Middle East), 1% to 2% [Oceania (Australia and New Zealand)] and 0.8% to 7.6% (Asia). Compared with these rates, the MDR-TB rate of 44%, reported from the Gizan area of Saudi Arabia, was the highest rate overall. A possible explanation for this extremely high rate has been discussed earlier. Even when this high MDR-TB rate is excluded from the general picture, the MDR-TB rate in Saudi Arabia is still high, ranging from 1.5% to 25.7%, thus placing Saudi Arabia firmly among those countries with the highest MDR-TB rates.

It is difficult to draw any strong conclusions about the status of drug-resistant TB in this country from these studies, for several reasons:

Apart from possible variations in the populations studied, geographical origin of the patients, site of M. tuberculosis isolation (pulmonary or extrapulmonary), and patient compliance with treatment, the cause of this apparent discrepancy in prevalence of drug-resistant TB in different regions of Saudi Arabia remains unclear.

In conclusion, this review highlights the need to develop a standardized national policy for surveillance of drug-resistant TB in Saudi Arabia. This could be achieved by establishing a network of national reference laboratories, using internationally accepted and standardized methods of susceptibility testing. Such a system would allow trends in antituberculosis resistance over time to be monitored, in accordance with the WHO and the International Union Against Tuberculosis and Lung Disease (IUATLD) guidelines [3].