Tubercle最新文献

This study reports the findings of an epidemiological survey of death due to avian tuberculosis in the captive collection of wildfowl at The Wildfowl and Wetlands Trust Centre, Slimbridge, Gloucestershire. Both genetic and environmental factors have been shown to affect the incidence of, and the birds' susceptibility to, the disease.

Seasonal body condition was related to the occurrence of death due to the disease in both males and females. Birds from either hot or cold climates appeared to have a higher incidence than those from temperate climates. What the birds ate did not affect incidence but the method they used for obtaining their food did. Higher susceptibility was found in those species evolved for marine or arboreal habitats. Anomalies in susceptibility which suggest a higher level of genetic immunity in some groups have also been found. Reasons are put forward to explain these findings.

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<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.

Resistance to six anti-mycobacterial agents rifampicin, isoniazid, streptomycin, ethambutol, p-amino salicylic acid and cycloserine was studied. Variations in the resistance pattern among Saudi, non-Saudi and a stable National Guard King Khaled Hospital (NGKKH) population were investigated. A high percentage of relapse cases, 21 %, was recorded. Among the NGKKH population this figure was much lower, 9.9%. Resistance to rifampicin alone was high at 7.2% followed by streptomycin 3.3%, isoniazid 1.8%, p-amino salicylic 1.2% and cycloserine 0.8%. Resistance to rifampicin alone was higher among ‘new’ cases whilst combined resistance to two or more drugs was seen more often in ‘old’ patients. Resistance was seen more frequently among non-Saudis, both ‘old’ and ‘new’. An unusual finding was the prevalence of rifampicin resistance among non-pulmonary isolates.

We outline the mechanisms contributing to the human form of the Koch phenomenon, which we define as necrosis occurring within 24–48 h of injection of mycobacterial antigen into the skin of past or present tuberculosis patients. It is probable that tissue damage mediated in the same way occurs in the lesions themselves. We suggest that the necrosis is mediated in part by cytokines, particularly Tumour Necrosis Factor (TNF), and that this occurs for three reasons. First, Mycobacterium tuberculosis evokes an immunoregulatory abnormality characterised by raised agalactosyl IgG. This abnormality, also found in rheumatoid arthritis, Crohn's disease, and Erythema Nodosum Leprosum, seems to be associated with dysregulation of cytokine release. Secondly, M. tuberculosis itself triggers further cytokine release. Thirdly, the normally protective role of TNF is distorted by several interacting properties of components of M. tuberculosis, which render the cytokine toxic to the host tissues.

The immunoregulatory abnormality may be susceptible to correction by immunotherapy.

The minimal inhibitory concentrations for 90% of strains (MIC90) of ofloxacin against Mycobacterium tuberculosis and Mycobacterium xenopi was 2 mg/I. This was three dilutions lower than that of pefloxacin and was well within the range of drug concentrations achievable in man. The antituberculosis activities of both quinolones were independent of resistance of the strains to other antimycobacteriaI agents. Mycobacterium avium-intracellulare was resistant to both compounds with MIC90s greater than 16 mg/l. The maximum serum levels (C_max) of both compounds increased proportionally with increasing dose size. The terminal elimination half-life ($\text{T}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$) of pefloxacin was longer than that of ofloxacin, but the $\text{T}{}_{\mathrm{<mtext>1</mtext><mtext>2</mtext>}}$ of both compounds in mice were much shorter than in man. The area under the concentration curve (AUC) of pefloxacin was double than that of ofloxacin. In the mouse, pefloxacin at doses up to 150 mg/kg daily was inactive against M. tuberculosis infection: in terms of survival rate the minimal effective dose of ofloxacin against M. tuberculosis infection was 150 mg/kg daily when given by gavage or by incorporation into the mouse diet at a concentration of 0.1 %, but in terms of cfu counts, ofloxacin 150 mg/kg daily only displayed a moderate degree of activity similar to ethambutol 100 mg/kg daily. The therapeutic effects of ofloxacin against M. tuberculosis infection were dose-related: 300 mg/kg daily by gavage or 0.4% in mouse diet displayed much better therapeutic effects than lower dosages. Since the AUC in mice treated with ofloxacin 150 mg/kg daily is close to that in man treated with a clinically tolerated dose—600 mg daily—such a dosage may be only moderately effective against human tuberculosis.