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.

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.

Visceral leishmaniasis in Gizan, Saudi Arabia.

Visceral leishmaniasis is endemic in southern Saudi Arabia. We prospectively evaluated 121 patients with visceral leishmaniasis at King Fahad Hospital in Gizan. All patients were infants and children. Seasonal variation was observed with more cases presenting in late spring and summer and few in winter. The predominant clinical features in these patients were chronic fever, abdominal distention, weight loss and hepatosplenomegaly. Lymphadenopathy was rare in contrast to African kala-azar. Common laboratory abnormalities included anemia, leukopenia, thrombocytopenia, hypoalbuminemia and hypergammaglobulinemia. Liver function tests were deranged in one-third of patients. Leishmania hemagglutination test was positive in all patients and all of them had positive bone marrow smear or culture for Leishmania donovani. Patients responded well to stibogluconate (Pentostam) therapy with a cure rate of 96.7%. Four patients died in the first few days of therapy. Jaundice and grossly deranged liver function tests were found to be bad prognostic signs.

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.

Detection of mycobacterial antigens in sputum by an enzyme immunoassay.

An enzyme immunoassay (EIA) for the detection of mycobacterial antigens in sputum was evaluated. The system utilises commercially available anti-BCG immunoglobulin. BCG protein standard was used as positive control. Thirty-nine patients with culture-proven pulmonary tuberculosis were tested. The EIA was positive in 24 of 29 patients with positive smears and cultures, giving a sensitivity of 86.2%. It was also positive in six of ten patients with smear-negative culture-positive disease, resulting in a sensitivity of 60% in this group. In another 176 patients with different nontuberculous pulmonary infections, only nine were positive by EIA, giving a specificity of 94.9%. The high sensitivity and specificity of the assay make it a useful tool for the early diagnosis of pulmonary tuberculosis.

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.

Tuberculin survey in the Eastern Province of Saudi Arabia.

We present the results of the Mantoux test (5 units tuberculin) survey in the Eastern Province of Saudi Arabia, which was conducted as part of a nationwide epidemiological survey of tuberculosis. A total of 1105 subjects were screened out of whom 630 gave a history of BCG vaccination in the past and 363 were BCG-negative. Among BCG-negative children aged 5-14 years, only 5% had a positive Mantoux, a rate lower than most Third World countries but higher than developed countries were under 2% of children are tuberculin reactors. This calls for continuation of free treatment of active cases and increased efforts towards screening of contacts. The results also vindicate the current policy of giving BCG vaccine at birth and probably indicates the need to revaccinate at school leaving age, in accordance with WHO recommendations. Tuberculin reactivity rose steeply with age (32% at age 15-24 and 72% at age 45-64 years) indicating the presence of a large pool of subjects at risk of breaking into active disease. Finally, 71% (201/283) of children aged 5-14 years who had received BCG vaccine at birth, reacted negatively to the Mantoux test. This supports the findings of previous studies that in the majority of subjects, BCG-induced tuberculin sensitivity fades a few years after vaccination.

Effect of initial isoniazid resistance on response to chemotherapy of tuberculosis: A review of clinical trials.

This study evaluated seventeen clinical trials of short-course chemotherapy of tuberculosis and assessed the influence of initial resistance to isoniazed on the response to therapy. High failure rates were observed for the non-rifampicin-containing regimens. When rifampicin was included, there was a very good response among patients suffering from sensitive and resistant strains. Regimens that included both rifampicin and pyrazinamide yielded the best results, with low failure rates observed for sensitive and resistant patients. The addition of streptomycin and ethambutol to these regimens did not improve the response in patients with isoniazid-resistant bacilli. Prolonged therapy generally yielded a better response; however, in rifampicin-containing regimens, the use of pyrazinamide for more than two months did not influence the outcome of therapy. In patients with isoniazid-resistant strains, 4- and 6-month regimens containing rifampicin and pyrazinamide both yielded low failure rates. Initial isoniazid resistance had very little impact on the response to such regimens when therapy was carried out for 6 months.

Failure of ciprofloxacin to eradicate brucellosis in experimental animals.

Ciprofloxacin is a quinolone that penetrates well intracellularly. It was shown to be active against Brucella melitensis in vitro. In this study, ciprofloxacin and tetracycline were used to treat B. melitensis and B. abortus infections in mice. The drugs were given for 7, 14, 21 and 28 days. Tetracycline reduced spleen and liver weight and splenic bacterial counts and eliminated the infection in 70% of mice treated for 3 or 4 weeks. Ciprofloxacin, on the other hand, did not affect liver or spleen weight or bacterial counts after 3-4 weeks of therapy. It failed to eradicate the organism from any of the mice treated. It is concluded that ciprofloxacin is probably not suitable for the treatment of brucellosis.

Drug resistance in tuberculosis.

Resistance to antituberculosis drugs is due to the occurrence of resistant mutants in the bacterial population even before exposure to these drugs. These mutations are chromosomal in origin. Resistance occurs when the bacterial population is large or when drugs are used alone. Potent drugs such as rifampicin, isoniazid and streptomycin are effective in preventing emergence of resistance. Resistance to isoniazid and streptomycin was found to have minimal influence on response to short-course chemotherapy. On the other hand rifampicin resistance was associated with a high failure rate. Control of resistance is important to maintain the success of short-course chemotherapy. The restriction of the use of rifampicin to treatment of tuberculosis in combined drug regimens will reduce the occurrence of resistance to this essential drug.

Nosocomial bacteraemia in a teaching hospital in Saudi Arabia.

During a period of one year, 117 episodes of nosocomial bacteraemia were documented at King Khalid University Hospital, an incidence of 5 per 1000 admissions. Sixty-two percent were gram-negative organisms with Escherichia coli, Klebsiella spp., Serratia spp. and Pseudomonas spp. being the most frequent. Staphylococcus aureus was the most common gram-positive organism isolated. The source of infection was identified in 75% of patients. Intravenous lines accounted for a high proportion of cases (22%). Most deaths occurred in infants and patients with serious underlying disease.

Resistance to antituberculosis drugs in Riyadh, Saudi Arabia.

The prevalence of resistance to antituberculosis drugs in Riyadh was found to be 21.3%, while the rate of primary drug resistance was 11.5%. Resistance to isoniazid was the most common (19.4%) followed by rifampicin and streptomycin. The prevalence of primary and acquired rifampicin resistance was 3 and 33.7% respectively. The majority of isolates from patients with acquired resistance to rifampicin were resistant also to isoniazid.

Joint mobility and mitral valve prolapse in an Arab population.

The association of joint laxity and mitral valve prolapse (MVP) has been disputed. In this study of an Arab population, the joint mobility scores of 29 subjects with MVP, 10 of whom were asymptomatic, were compared to 60 normal controls. It was found that the joint mobility score was significantly higher in both the asymptomatic and the symptomatic subjects with MVP when compared to the controls. This suggests that both mitral valve prolapse and joint laxity may be due to the same abnormality of connective tissue structure.

Brucella meningitis.

Infection with Brucella melitensis is endemic in Saudi Arabia but involvement of the central nervous system (CNS) is rare. We report on three patients with acute brucella meningitis, all of whom had a history of exposure to a possible source of infection. Diagnosis was confirmed by isolation of Brucella species from blood cultures. Examination of cerebrospinal fluid revealed lymphocytic pleocytosis with a high concentration of protein and low concentration of glucose. The patients were treated by combinations of co-trimoxazole, doxycycline or rifampicin. All responded well without recurrences. A combination of two of the three drugs was effective in treating brucellosis of the CNS when given for a period of 6-8 weeks.

Heat stroke at the Mekkah pilgrimage: clinical characteristics and course of 30 patients.

The clinical picture and the final outcome of 30 patients with heat stroke during the Mekkah pilgrimage 1404 (September 1984) were analysed. Rapid cooling by the 'evaporative method' was achieved in a mean time of 59 min (range 15-135). An initial temperature above 42 degrees C and a cooling time of more than 1 h indicated a poor prognosis. Acute hepatic failure, 'adult respiratory distress syndrome' and decerebrate convulsions were among the fatal complications occurring in three patients. In the final outcome three patients (10 per cent) died, two patients (7 per cent) recovered but developed myocardial infarction and cerebellar ataxia respectively. Twenty-five patients (83 per cent) made an uncomplicated recovery.