Tuberculosis (TB) is the second leading cause of death from an infectious disease worldwide, after the human immunodeficiency virus. There are almost 2.5 million new smear-positive pulmonary TB cases and 1.9 million new smear-negative pulmonary TB cases in the world in 2012 according to the World Health Organization (WHO) Global Tuberculosis Report 2013. Smear negativity in pulmonary TB is a common clinical problem. Clinicians have difficulty in diagnosing smear-negative pulmonary TB without bacteriological confirmation. It is very important to decide whether or not to treat a patient with smear negative pulmonary TB when the culture results are pending or negative. New diagnostic methods are required for the diagnosis of smear-negative pulmonary TB. In addition to the development of new microbiological and serological diagnostic tests, clinical prediction scoring systems and algorithms including clinical and radiological findings of smear-negative pulmonary TB patients in our country, should be established to facilitate the diagnosis of smear-negative pulmonary TB.
A retrospective study of factors associated with poor patient compliance with antituberculosis therapy was conducted in Taiping, Perak. 219 patients were studied. Male patients and hospital referrals were significantly more likely to default. Patients with tuberculous lymphadenitis alone had a greater rate of default, but this just failed to reach significance (0.05 < p < 0.10). Six of 7 male hospital referrals with tuberculous lymphadenitis alone defaulted. Patients treated as outpatients from the start were more compliant. Housewives were also highly compliant. It was noticed that patients who defaulted tended to do so during early stages of treatment.
The aim of this study was to determine whether simultaneous and sequential skin testing with tuberculin and sensitins give consistent results. A total of 475 8- or 9-year-old schoolchildren were skin tested sequentially, at an interval of 3 days, with PPD tuberculin and with either Mycobacterium scrofulaceum or M. avium sensitin. The results were compared with those of 470 simultaneously tested children chosen from the same living area. There were no statistically significant differences between the frequencies of the reactions of sequentially and simultaneously tested children. When the sequential testing procedure was employed, 3.1% reacted to tuberculin, 19% to M. avium sensitin and 30% to M. scrofulaceum sensitin, taking a 6 mm cut-off. The corresponding figures for the simultaneously tested children were 4.7, 21 and 36%, respectively. Thus, there was no indication that the simultaneous testing procedure in itself influenced the results, neither was there any sign of a booster effect when testing in sequence with an interval of 3 days in non-BCG-vaccinated children.
The prevalence and incidence of active tuberculosis among 21,959 recently arrived (1982-1985) immigrants from 7 selected Asian countries into British Columbia (BC), Canada, were reviewed. Among these newly arrived immigrants, 1173 (5.3%) were judged to have inactive tuberculosis at the immigration examination in their country of origin. In this subgroup, 14 of 932 (1.5%) were found to have active tuberculosis at the initial examination after arrival in Canada. Subsequently, 7 further cases arose in this group of inactive cases giving an average annual incidence rate of 0.33% over the 4-year period of study. Only 3 of these 21 cases had had previous antituberculosis chemotherapy. The remaining 20,786 recent immigrants with normal X-rays at the immigration examination contributed 30 cases during the next 4 years--an average annual incidence rate of 0.08% or 8 times the comparable rate for BC (0.01%). The limitations of the immigration screening process are illustrated and the value of early surveillance of immigrants designated as having inactive tuberculosis is underlined. The apparent failure to exclude active disease prior to the arrival of these immigrants is one factor elevating the incidence of active tuberculosis in the first few years after arrival in the host country. Other factors include the relatively high prevalence of inactive tuberculosis among the immigrants from certain countries and their high rate of early relapse after entry, especially in those not previously treated. Such immigrants should be considered for chemoprophylaxis immediately after entry.
In 1989/90 the WHO Tuberculosis Unit undertook a special study to determine the nature and magnitude of the global tuberculosis problem by reviewing the official statistics and the available data from both published and unpublished field studies. The findings revealed that about 1700 million people or one-third of the worlds population are or have been infected with Mycobacterium tuberculosis with 8 million new cases found in developing and industrialized countries. It estimated that the disease caused 2.9 million deaths in 1990 making this the largest cause of death from a single pathogen in the world. While the largest number of deaths occurred in the Southeast Asian Region (940000) the Western Pacific Region (890000) and the African Region (660000) it is estimated that more than 40000 deaths still occur annually in the industrialized nations. Given the existing tuberculosis situation in the world the WHO has developed a new tuberculosis control strategy the development of which was based on a series of workshops and case studies in the last 2 years. These strategies include: 1) the introduction of short-course chemotherapy in place of the standard chemotherapy to improve the cure rate; and 2) the expansion of tuberculosis services.
Isolated splenic abscesses is an uncommon clinical entity that is being increasingly recognized as a cause of intraabdominal sepsis in a wide variety of clinical situations, and involving a wide range of organisms. The increasing incidence of immunosuppressed states in this decade due to the use of chemotherapy for oncology, immunosuppression therapy for transplantation, and acquired immune deficiency syndrome, has changed the disease pattern of splenic abscesses.Data from 287 cases reported in the English literature between 1987 and 1995 were collected, analyzed, and compared with two previous reviews of cases reported before 1987. results: Staphylococcus, Salmonella, and Escherichia coli are the most common organisms cultured. Immunosuppressed states were present in 33.5% of cases, with intravenous drug abuse and acquired immune deficiency syndrome accounting for half these cases. Computerized tomography and ultrasonography are diagnostic, with a sensitivity of 92.2% and 87.2%, respectively. Nonoperative management has a success rate of less than 65%, but salvage splenectomy does not increase mortality compared with splenectomy as initial therapy.Splenic abscesses are increasingly recognized with immunosuppressed states. Percutaneous radiologically guided drainage may be suitable in some cases, but splenectomy with appropriate antibiotics is the definitive treatment.
This review, the third in the series on cellular immune reactivity to tubercle bacilli in the centenary year of Koch's classical paper describing this phenomenon and its possible implications [1], represents an immunogenetic point of view. In fact this will be quite a broad point of view by an immunogeneticist who is not hampered by specific knowledge on therapy or prevention of tuberculosis. In this respect I probably do not differ very much from Robert Koch 100 years ago! An important difference, however, is that we think we now understand a great deal of the cellular and molecular basis of the immunological phenomena observed by Koch. Immunogenetics has contributed considerably to our current understanding and I will try to review that contribution here. Because thus far my main research interest has been in another mycobacterium, namely Mycobacterium leprae, I will use M. leprae and leprosy as an example to illustrate some ideas. The message of this review is that there is a reason for optimism: the knowledge recently gained by cellular and molecular immunologists as well as immunogeneticists has straightforward implications for the rational development of subunit vaccines and immunotherapeutic strategies.
The epidemiology of mycobacterial infections was studied in a wide cross-section of the Jeddah population over 2 years (1987-1989). Saudis, non-Saudis and patients from a stable population attending National Guard King Khalid Hospital (NGKKH) were compared. The ratio of Saudi to non-Saudi was 1:2 and males accounted for 65% of the total. The incidence was highest among young adults although the peak varied slightly between Saudi and non-Saudi patients. Extra-pulmonary tuberculosis was also preponderant among young adults, particularly females. Variants of Mycobacterium tuberculosis were investigated for the first time in Saudi Arabia. African and Asian variants were isolated from both Saudi and non-Saudi patients, the former being more numerous. Extra-pulmonary tuberculosis, particularly lymphadenopathy, accounted for a large proportion of mycobacterial infections, 59% at NGKKH. Mycobacterial species other than M. tuberculosis were fully identified and accounted for 9% of the isolates, Mycobacterium fortuitum and Mycobacterium chelonei being the two most prevalent.
The reemergence of tuberculosis,including the impact of HIV infection and multidrug- resistant tuberculosis, have renewed interest in the bacille Calmette-Guerin (BCG) vaccine. During the past 7 decades, numerous studies have shown variable efficacy of BCG vaccination, ranging from 0% to 80%. The BCG vaccine is more likely to prevent disseminated forms of tuberculosis in children than pulmonary tuberculosis in adolescents or adults. Bacille Calmette-Guerin vaccination is recommended in asymptomatic children with or at risk for HIV infection, but it rarely may cause disseminated BCG infection and should not be used in persons with symptomatic HIV infection or AIDS. In healthcare workers with exposure to Mycobacterium tuberculosis, including multidrug-resistant tuberculosis, BCG vaccination generally is not recommended. Revaccination with BCG does not confer more benefit than initial vaccination, and repeat vaccinations should be discontinued. With recent advances in technology and a better understanding of the immunopathogenesis of tuberculosis, efforts to develop a more potent and specific vaccine need to be pursued. If a more effective vaccine against tuberculosis is developed, vaccination can be expected to have an additional impact on global tuberculosis control in conjunction with current strategies of case detection, treatment of disease, and preventivetherapy.
A working group (FEBIM) within the European Organisation for Research and Treatment of Cancer undertook extensive studies on the possible association of infectious diseases and the risk of malignant melanoma. These studies provided evidence that several infectious diseases and also some vaccines including the anti-tuberculosis vaccine, BCG, derived from Mycobacterium bovis, confer a significant level of protection against this form of cancer. In recent years, the importance of immunoregulatory networks in the establishment of tolerance to tumour antigens and the key role of the innate immune system in the development of such networks have been recognised. The molecular patterns of micro-organisms activate pattern recognition receptors on antigen presenting cells and determine the qualitative nature of the ensuing immune response. Bacteria in the actinomycetales family, notably members of the genus Mycobacterium, exhibit particularly powerful adjuvant activity and profoundly affect underlying patterns of immune reactivity. In particular, there is growing evidence that a heat-killed preparation of a strain of Mycobacterium vaccae is able to down-regulate patterns of immune reactivity that favour the tumour and to induce those that lead to anti-cancer immune responses. The results of preliminary clinical observations with melanoma patients, and published studies on other cancers, point to the need for more formal clinical trials.
A case of subclinical disseminated intravascular coagulopathy due to antituberculosis drugs, probably rifampicin, is described. The patient also developed marked leucocytosis, a 'flu-like illness, intravascular haemolysis, and acute renal failure as part of the drug reaction.
Sputum and faeces were obtained from 276 patients on admission to a study of drug resistance in Hong Kong. Acid-fast bacilli were detected microscopically in 103 (37%) sputum specimens and 135 (49%) yielded Mycobacterium tuberculosis on culture. Three methods were used to decontaminate faeces prior to dilution and culture in selective liquid Kirchner medium. A total of 61 faecal specimens were positive for M. tuberculosis on culture and, of these, pretreatment with sodium hydroxide yielded 60 (98%), Portaels modification of Wolinsky and Rynearsons's method 28 (46%) and the combined use of benzalkonium chloride and 1-hexdecylpyridinium chloride yielded 32 (52%). It is recommended that faeces should be treated with sodium hydroxide followed by dilution and culture in selective media, although it may be necessary to formulate new selective media for mycobacterial species other than M. tuberculosis.
CFLP mice were infected intravenously with Mycobacterium tuberculosis strain H37Rv and the progress of chemotherapy was followed by counts of viable bacilli in the lung and spleen. After spleen counts had reached log10 7.0, 12 experimental groups, each containing 10 mice, were treated for 8 weeks with pyrazinamide (PZA) given in mean daily dosages of 100, 200 or 400 mg/kg/day, with the interval between the doses within each dosage group being 1, 2, 4 or 8 days. All mice were also given 25 mg isoniazid/kg daily. An increase in the mean daily dosage from 100 mg PZA/kg to 400 mg PZA/kg resulted in a decrease of spleen viable counts at the end of treatment from log10 4.2 to log10 3.8. The organ counts, averaged over the full dosage range, were little altered by spacing out the interval between doses from 1-4 days, while increasing dose size proportionately: the counts with low mean dosages tended, however, to decrease (indicating improved efficacy) while those with high mean dosages increased (P less than 0.001). Counts increased when the interval was 8 days. Spacing out the doses while keeping the dose size constant resulted in progressive loss of efficacy. These findings suggest that, if PZA is given intermittently, the size of the dose should be increased, though not quite proportionately, to maintain full efficacy. Even with such an increase in dose, however, once weekly treatment would be less effective.
To examine the current practices and attitudes of health workers to the prevention of tuberculosis in our 55-bed chest unit, we investigated the tuberculin reactor status, reviewed pre-employment screening and reviewed the action taken after contact with tuberculosis by staff members. We assessed all 61 staff members, including 44 nurses, 1 physiotherapist, 11 doctors and 5 domestic workers. 47/61 staff members had had BCG vaccination. Heaf testing revealed 3 Heaf-negative subjects and, of the remainder, 52 had grade 3 or stronger reactions. Only 3/11 doctors, 36/44 nurses and 4/5 domestic workers had had any pre-employment screening. No action was taken by any doctor after their last contact with tuberculosis, whereas 10/44 nurses and 3/5 domestic workers had had chest X-rays. This study shows the low importance with which the risk of tuberculosis is perceived, particularly by doctors and demonstrates the need for stricter supervision and improved quality of pre-employment screening.
Mycobacterium avium-intracellulare (MAI) can utilize paraffin wax as the sole carbon source in basal media. Paraffin slide culture (Para SL/C) has been employed for isolation and speciation of MAI derived from clinical sources. We have evaluated an adaptation of this method for antimicrobial sensitivity testing. Sixteen clinical isolates of MAI were tested against ciprofloxacin amikacin, and azithromycin by Para SL/C and compared with sensitivities obtained with a conventional broth microtiter procedure. The system can be performed rapidly over a median time interval of 6-8 days. The MIC was defined as the lowest concentration of antimicrobial agent necessary to inhibit growth on paraffin wax coated slides. With Para SL/C, the MIC values were determined at the time when the corresponding control tubes showed confluent growth. The procedure was reproducible with all of the agents tested. The MIC50 and MIC90 values obtained from the Para SL/C assay and from serial broth microtiter dilutions correlated well for ciprofloxacin and amikacin. However, results of the MIC50 and MIC90 for azithromycin did not correlate.
In vitro antimicrobial activity of fleroxacin (6,8- difluoro-1-(2-fluoroethyl)-1, 4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid) and ofloxacin against representative pathogenic mycobacteria was evaluated by the agar dilution method, using 7H11 agar medium. Fleroxacin showed appreciable antimicrobial activity against Mycobacterium tuberculosis (MIC90 = 6.25 mg/l), M. kansasii (MIC90 = 3.13 mg/l), and M. fortuitum (MIC90 = 6.25 mg/l), whereas M. marinum, M. scrofulaceum, M. avium, M. intracellulare, and M. chelonae were highly resistant to the agent. The activity of fleroxacin was comparable to that of ofloxacin. Fleroxacin showed antimicrobial activity against M. intracellulare phagocytosed in murine peritoneal macrophages at a concentration of 10 mg/l in the culture medium, but its activity was considerably lower than that of ofloxacin. On the other hand, the therapeutic activity of fleroxacin against M. fortuitum infection induced in mice was higher than that of ofloxacin. Neither fleroxacin nor ofloxacin was efficacious against M. intracellulare infection. Fleroxacin significantly depressed the growth of M. leprae in the mouse footpad.
A 33-year-old man with AIDS and pleuro-pulmonary tuberculosis was treated with a combination of antituberculous medications for 12 months and with continuation of isoniazid. A total of 2 months after completing combination therapy the patient developed fever, malaise, and anorexia. Mycobacterial blood cultures grew M. tuberculosis and the patient improved with the readministration of rifampicin and pyrazinamide. Phage typing of the patient's isolates of M. tuberculosis confirmed that he had experienced a relapse and not a reinfection. The patient had received 5 months of his treatment while hospitalised. We believe he was compliant with therapy outside the hospital because he attended all of his clinic appointments. Follow-up studies of HIV-infected patients with tuberculosis are therefore needed.
