Progressive rise of Mycobacterium tuberculosis resistance to rifampicin and streptomycin in Riyadh, Saudi Arabia.

OBJECTIVE: The aim of this study was to investigate, for the first time, the factors associated with resistance to antituberculous drugs in Saudi Arabia, and to follow the long-term trends in drug resistance. METHODOLOGY: A retrospective study of patients with positive Mycobacterium tuberculosis recorded at the Riyadh Tuberculosis Center in 1990 was undertaken. The resistance figures from the same centre for the period July 1996 to June 1997 were reviewed for comparison. RESULTS: Resistance was significantly higher in those previously treated (71%) than in those who denied previous treatment (34%). There was a trend towards association of resistance with cavitatory, multilobar, and acid fast bacilli-positive cases. Nationality (Saudis, Yemenis, others) had no significant effect on resistance. The Riyadh Region now has the same high prevalence of rifampicin resistance as previously reported in the Western Region of the Kingdom. The figures on resistance for the years 1986-88, 1990, and 1996-97 were: isoniazid 19.5/13.8/11.1%, rifampicin 10/20.7/24.6%, streptomycin 5/22/27.4%, ethambutol 3.7/3.9/1.8%, respectively. The reduction in isoniazid and ethambutol resistance coincided with a rise in resistance to rifampicin and streptomycin. We speculate that this resulted from the fact that isoniazid and ethambutol are restricted only to the treatment of tuberculosis and cannot, by law, be dispensed by general practitioners or private pharmacies. Rifampicin and streptomycin, however, are widely used for brucellosis; an endemic disease in Saudi Arabia where up to 12 weeks of rifampicin therapy is recommended. CONCLUSIONS: There has been a significant increase in rifampicin and streptomycin resistance in Saudi Arabia over the last 10 years. Possible causes include poor compliance and wide use of these two drugs for non-tuberculosis conditions. These findings could jeopardize the benefits of the directly observed therapy short course policy which is being implemented in Saudi Arabia. Consideration should be given to prohibiting the routine use of rifampicin for the treatment of brucellosis.

Clinical profile of sleep apnea syndrome. A study at a university hospital.

OBJECTIVES: To review a series of patients with sleep apnea syndrome, to promote more awareness and alert local health professionals to early diagnosis and treatment. METHODS: We studied, prospectively, 48 consecutive patients who were managed at the university hospital from 1992 to 1996. RESULTS: The male:female ratio was 1.4:1. The mean interval between onset of symptoms and the diagnosis was 5.5 years (range 0.25 to 30). In over half of the patients the diagnosis was not suspected upon referral. The mean body mass index was 42.8 kg/m2, (range 25 to 76). Daytime hypoxemia was present in 28 patients (58%), while 26 (54%) had Pa CO2 > 45 mmHg, mainly as a result of obesity-hypoventilation syndrome. Significant proportions had systemic and pulmonary hypertension (60% and 23%), and 32% had ischemic heart disease. All patients, but one, tolerated continuous positive airway pressure, but cost of the equipment led some to prefer surgical treatment that is offered free. CONCLUSION: This series shows a bias towards female sex and frequent association with obesity-hypoventilation syndrome. In many cases the diagnosis was not suspected suggesting poor recognition and awareness of sleep apnea syndrome. Monitoring pulse oximetry during sleep was helpful in the diagnosis and titration of continuous positive airway pressure. Ways of providing continuous positive airway pressure under the health system need to be studied.

Improved sensitivity for detection of tuberculosis cases by a modified Anda-TB ELISA test.

Tuberculosis is still a major health problem in most developing countries and its incidence is rising in many industrial countries. The diagnosis of tuberculosis depends primarily on identification of mycobacteria and on clinicoradiological evidence of the disease. Compared to other diagnostic methods, serological tests are faster and do not necessarily require samples that contain the tubercle bacilli. We have evaluated a modified version of a commercially available enzyme immunoassay test to detect the presence of circulating anti-mycobacterial IgG and IgM antibodies in tuberculosis patients. The sensitivity and the specificity of the test reaches 87% and 95% respectively. In conclusion, the modified Anda-TB enzyme immunoassay test offers a good and reliable test for diagnosis of tuberculosis in suspected cases of active pulmonary tuberculosis.

Communication with the seriously ill: physicians' attitudes in Saudi Arabia.

OBJECTIVES: To study some ethical problems created by accession of a previously nomadic and traditional society to modern invasive medicine, by assessment of physicians' attitudes towards sharing information and decision-making with patients in the setting of a serious illness. DESIGN: Self-completion questionnaire administered in 1993. SETTING: Riyadh, Jeddah, and Buraidah, three of the largest cities in Saudi Arabia. SURVEY SAMPLE: Senior and junior physicians from departments of internal medicine and critical care in six hospitals in the above cities. RESULTS: A total of 249 physicians participated in the study. Less than half (47%) indicated they provided information on diagnosis and prognosis of serious illnesses all the time. Physicians who were more senior and those who spoke Arabic fared better than other groups. The majority (75%) preferred to discuss information with close relatives rather than patients, even when the patients were mentally competent. Most of the physicians (72%) felt patients had the right to refuse a specific treatment modality, and 68% denied patients the right to demand such a treatment if considered futile. Further analysis showed that physicians' attitudes varied along a spectrum from passive (25%) to paternalistic (21%) with the largest group (47%) in a balanced position. CONCLUSIONS: In traditional societies where physicians are regarded as figures of authority and family ties are important, there is a considerable shift of access to information and decision-making from patients to their physicians and relatives in a manner that threatens patients' autonomy. Ethical principles, wider availability of invasive medical technology and a rise in public awareness dictate an attitude change.

Does the protective effect of neonatal BCG correlate with vaccine-induced tuberculin reaction?

A case-control study was conducted in Saudi Arabia, where the same strain of BCG has been used and surveys had shown that up to 88% of vaccinated children remain tuberculin negative. Active cases were obtained by surveying the seven tuberculosis centers in 1 yr. Control subjects were obtained from a nationwide survey of normal individuals. Vaccination in both groups was ascertained by history and BCG scar. Relative risk of contracting active tuberculosis in the vaccinated versus unvaccinated and protection was calculated. Protection was as follows: age group 5 to 14 yr, 82% (55 to 93%); age group 15 to 24 yr, 67% (55 to 77%); and age group 25 to 34 yr, 20% (-6 to 37%). We document the uninterrupted record of protection by BCG administered in the neonatal period and discuss the significance of vaccination timing. We concur with other studies that protection lapsed after about 20 yr. More importantly, this is the first large study that documents a lack of tuberculin sensitivity despite protection. This challenges the view that sensitization is essential for protection and supports the "two-pathway" theory that BCG vaccination could trigger either protective (Lister type) or antagonistic (tuberculin or Koch type) reactions and that the most protective vaccines would have little tuberculin-sensitizing effect because the two pathways are competitive.

Tuberculosis presenting as immune thrombocytopenic purpura.

Various haematological abnormalities commonly occur in active tuberculosis (TB). However, thrombocytopenia is rare and immune thrombocytopenic purpura (ITP) is mentioned only in few case reports. We found that of 846 cases with active TB, 9 (1%) presented with ITP as the only abnormality. Three out of these 9 cases had disseminated miliary TB, 3 an abdominal abscess or lymphadenitis, and 3 pulmonary TB; none had palpable splenomegaly. All patients had purpura and the platelet count varied between 4 and 21 x 10(9)/l, and the bone marrow showed increased megakaryocytes. All tuberculous patients showed initially a poor platelet count response to steroid therapy. The platelet count returned to normal 2-6 weeks after oral prednisone combined with antituberculous drugs.

Effect of moderately high altitude on the pattern of lung disease.

In high altitude areas, inspired atmosphere oxygen decrease proportionally to the vertical distance from sea level. Population in these areas some adaptive mechanisms to cope with the relatively hypoxic environment. This study compares populations who live in highland areas (2500 meters above sea level) with those in lowland areas (close to sea level). No differences were observed in the prevalence or mortality rate of respiratory diseases between these two groups. It is concluded that even if adaptive mechanisms can be observed in dwellers of moderately high altitude (<3000 m above sea level), such altitude does not adversely affect the pattern of respiratory disease in these populations. However, partial pressure of oxygen (PaO2) tends to be lower in individuals of high altitude areas, leading to marked oxygen desaturation when such individuals encounter a significant respiratory illness. Physicians are advised to introduce early and effective therapeutic measures before such deterioration occurs.

Nationwide community survey of tuberculosis epidemiology in Saudi Arabia.

In the first nationwide community-based survey of the epidemiology of tuberculosis in Saudi Arabia, 7721 subjects were screened in the 5 provinces (using an equal proportional allocation formula) for 2 parameters: (1) prevalence of positive Mantoux test in non BCG vaccinated subjects; (2) prevalence of bacillary cases on sputum culture. The prevalence of positive Mantoux reaction in children aged 5-14 years was 6% +/- 1.8; higher in urban areas (10%), and lower in rural areas (2%), thus classifying Saudi Arabia among the middle prevalence countries. These relatively good results (by Third World standards) could reflect the rise of the standard of living and wide availability of free treatment for active cases with a lowered risk of infection in the community. This view is supported by the fact that in our survey, only one subject grew Mycobacterium tuberculosis in the sputum. However, there were foci of high prevalence of Mantoux reaction in the urban communities in the Western province (20% +/- 8.7 urban; 1% +/- 1.9 rural). The problem may be caused by the fact that the province receives every year over a million pilgrims, some of whom are known to settle illegally and escape the usual screening for tuberculosis imposed on foreign labourers. In conclusion, even in the absence of an enforceable national programme for the eradication of tuberculosis, the economic standard and wide availability of free treatment for active cases has resulted in relatively low rates of prevalence of tuberculin sensitivity in children. The foci of high prevalence in the Western Province require special screening arrangements.

The significance of positive Mantoux reactions in BCG-vaccinated children.

As the interpretation of tuberculin skin tests is controversial in subjects who have received BCG vaccine, we administered Mantoux tests to 2588 randomly selected Saudi children aged 5-13, 1945 of whom had been vaccinated with BCG at birth and 643 were unvaccinated. Only 7.8% of the BCG-vaccinated children were Mantoux positive (greater than or equal to 10 mm induration) at the age of 5 years, which was not significantly different from the unvaccinated children. The tuberculin sensitivity rose more steeply with age in the BCG-vaccinated than the unvaccinated children so that the difference between both groups became statistically significant in those aged 12 and 13 (20% versus 3.9%, 15.5% versus 4.1% respectively). These findings support the previously expressed theoretical postulates that BCG-vaccinated subjects display an increased ability to respond immunologically to encounters with environmental mycobacteria. In communities with low prevalence of environmental mycobacteria, this would result in a slow but persistent rise of skin reactivity to tuberculin which, if given time, will become greater than that of unvaccinated subjects.

Diagnostic role of fibreoptic bronchoscopy in tuberculosis in the presence of typical X-ray pictures and adequate sputum.

Fibreoptic bronchoscopy (FOB) showed that of 82 patients who had 'typical' X-ray pictures of tuberculosis (fibronodular infiltrate in the upper lobe), 40 had active tuberculosis, 30 had inactive tuberculosis and 12 had non-specific fibrosis of undetermined origin. The remaining 16 patients with other specific aetiologies of the upper lobe lesions (e.g. carcinoma) had different X-ray pictures such as a mass or alveolar filling of lobar distribution. In communities with a high prevalence of tuberculosis FOB is therefore unlikely to reveal any specific aetiology (apart from tuberculosis) in immunologically competent patients who have 'typical' X-ray picture of tuberculosis. We document, however, that in sputum-producing patients with active tuberculosis, FOB was the exclusive means of diagnosis in 11/27 (41%), compared with 10/13 (77%) in non-sputum-producers. An immediate diagnosis was made in 22% and 38% of cases respectively.

The chest radiograph in brucellosis.

A retrospective study of chest radiographs in patients with brucellosis was undertaken at King Khalid University Hospital, Riyadh. The commonest presenting symptoms were fever, back and joint pains, excessive sweating, headache, and cough. Different chest radiographic abnormalities were detected, including soft miliary mottling, parenchymal nodules, consolidation, chronic diffuse changes, hilar or paratracheal lymphadenopathy and pneumothorax. Soft miliary mottling and pneumothorax have not been described before. The high incidence of lung abnormalities is most probably due to the chronicity of the disease in the present series.