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Biomedical subjects

I Bastian

Publications and source records attributed to I Bastian.

At least 19 recordsLinked to original sources

A review of the diagnosis and treatment of smear-negative pulmonary tuberculosis.

Recommendations on the management of smear-negative pulmonary tuberculosis (TB) are still based on the behaviour of this disease in populations unaffected by the human immunodeficiency virus (HIV). Studies prior to the HIV epidemic estimated that there were 1.22 cases of smear-negative and extra-pulmonary TB for each smear-positive case. Patients with smear-negative pulmonary TB were found to be less infectious and to have a lower mortality, but a significant proportion (50%-71%) progressed to active disease justifying treatment. Moreover, a wide variety of regimens also proved effective in the treatment of smear-negative disease in HIV-negative patients. The advent of HIV has changed many of these parameters. Countries affected by both HIV and TB have experienced a disproportionate increase in smear-negative disease. While apparently remaining less infectious than smear-positive cases, HIV-positive patients with smear-negative pulmonary TB are generally more immunocompromised, have more adverse drug reactions, and suffer higher mortality rates on treatment. Clinical decision-making has also been complicated because HIV co-infection broadens the differential diagnoses of smear-negative pulmonary TB to include diseases such as Pneumocystis carinii pneumonia (PCP), pulmonary Kaposi's sarcoma, and Gram-negative bacteraemia. Our approach to smear-negative pulmonary TB must therefore adapt to these changed parameters. Management algorithms based on several features (clinical symptoms, response to antibiotic trials, smear investigations, and chest radiography) have been developed to improve case detection. These algorithms must be validated in each locale because their performance will vary depending on numerous local factors such as the regional prevalence of PCP. Alternative methods of specimen collection, such as sputum induction, and processing must be evaluated. National tuberculosis programmes should also consider extending the use of rifampicin-based short-course chemotherapy (SCC) to new patients with smear-negative disease. This latter intervention, and the much-needed establishment of additional microscopy and culture facilities, will depend on increased financial and technical support from the international community.

AIDS-Related Opportunistic Infections↗

Directly observed treatment, short-course strategy and multidrug-resistant tuberculosis: are any modifications required?

Multidrug-resistant tuberculosis (MDRTB) should be defined as tuberculosis with resistance to at least isoniazid and rifampicin because these drugs are the cornerstone of short-course chemotherapy, and combined isoniazid and rifampicin resistance requires prolonged treatment with second-line agents. Short-course chemotherapy is a key ingredient in the tuberculosis control strategy known as directly observed treatment, short-course (DOTS). For populations in which multidrug-resistant tuberculosis is endemic, the outcome of the standard short-course chemotherapy regimen remains uncertain. Unacceptable failure rates have been reported and resistance to additional agents may be induced. As a consequence there have been calls for well-functioning DOTS programmes to provide additional services in areas with high rates of multidrug-resistant tuberculosis. These "DOTS-plus for MDRTB programmes" may need to modify all five elements of the DOTS strategy: the treatment may need to be individualized rather than standardized; laboratory services may need to provide facilities for on-site culture and antibiotic susceptibility testing; reliable supplies of a wide range of expensive second-line agents would have to be supplied; operational studies would be required to determine the indications for and format of the expanded programmes; financial and technical support from international organizations and Western governments would be needed in addition to that obtained from local governments.

Antitubercular Agents↗

Detection of rifampicin resistance in Mycobacterium tuberculosis isolates from diverse countries by a commercial line probe assay as an initial indicator of multidrug resistance.

The line probe assay (LiPA), a rapid molecular method for detecting rifampicin resistance (RMPr) in Mycobacterium tuberculosis, correctly identified all 145 rifampicin-sensitive (RMPs) and 262 (98.5%) of 266 RMPr strains among 411 isolates collected from diverse countries. If used as a marker of multidrug-resistant tuberculosis (MDR-TB), detection of RMPr by LiPA would have detected 236 of the 240 MDR strains in this study but would have wrongly suggested the presence of MDR in 26 RMP-monoresistant isolates (sensitivity 98.3%, specificity 84.8%). Hence, the reliability of using LiPA (or any other rapid RMPr-detection method) as a surrogate marker of MDR-TB largely depends on the prevalence of RMP-monoresistance in the study population. This approach must therefore be validated in each local situation.

Africa↗

Phylogenetic evidence for reclassification of Calymmatobacterium granulomatis as Klebsiella granulomatis comb. nov.

By sequencing a total of 2089 bp of the 16S rRNA and phoE genes it was demonstrated that Calymmatobacterium granulomatis (the causative organism of donovanosis) shows a high level of identity with Klebsiella species pathogenic to humans (Klebsiella pneumoniae, Klebsiella rhinoscleromatis). It is proposed that C. granulomatis should be reclassified as Klebsiella granulomatis comb. nov. An emended description of the genus Klebsiella is given.

Calymmatobacterium↗

Multicenter evaluation of the Abbott LCx Mycobacterium tuberculosis ligase chain reaction assay.

Four Australian hospital laboratories evaluated the performance of the Abbott LCx Mycobacterium tuberculosis assay with 2,347 specimens (2,083 respiratory and 264 nonrespiratory specimens) obtained from 1, 411 patients. A total of 152 specimens (6.5%) were culture positive for Mycobacterium tuberculosis complex (MTBC); of these, 79 (52%) were smear positive. After resolution of discrepant data, the overall sensitivity, specificity, and positive and negative predictive values for the LCx assay were 69.7, 99.9, 99.1, and 97.7% respectively. For smear-positive respiratory specimens that were culture positive for MTBC, the values were 98.5, 100, 100, and 98.4%, respectively, while the values for smear-negative respiratory specimens were 41.5, 99.9, 96.4, and 98%, respectively. Relative operating characteristic curves were constructed to demonstrate the relationship between sensitivity and specificity for a range of possible cutoff values in the LCx assay. These graphs suggested that the assay sensitivity for respiratory samples could be increased from 70.2 to 78.6%, while the specificity would be reduced from 99.9 to 99.4% by inclusion of a grey zone (i.e., LCx assay values of between 0.2 and 0.99). An algorithm is presented for the handling of specimens with LCx assay values within this grey zone.

DNA Ligases↗

Treatment and prevention of multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDRTB), which is defined as combined resistance to isoniazid and rifampicin, is a 'man-made' disease that is caused by improper treatment, inadequate drug supplies or poor patient supervision. Patients with MDRTB face chronic disability and death, and represent an infectious hazard for the community. Cure rates of 96% have been achieved but require prompt recognition of the disease, rapid accurate susceptibility results, and early administration of an individualised re-treatment regimen. Such regimens are usually based on a quinolone and an injectable agent (i.e. an aminoglycoside or capreomycin) supplemented by other 'second-line' drugs. This therapy is prolonged (e.g. 24 months), expensive, and has multiple adverse effects. Prevention of MDRTB is therefore of paramount importance. The World Health Organization (WHO) has recommended a multifaceted programme, known by the acronym DOTS (directly observed therapy, short-course), that promotes effective treatment of drug-susceptible TB as the prime method of limiting drug resistance. DOTS was part of a successful MDRTB control programme in New York City, which also included treatment of prevalent MDRTB cases, streamlined laboratory testing, effective infection control procedures and wider application of screening and preventive therapy (although the optimal chemotherapy for MDRTB infection remains undefined). Industrialised countries have the resources to treat patients with MDRTB and to mount these extensive control programmes. Unfortunately, MDRTB is also prevalent in Asia, South America and the former Soviet Union. First world countries have a vested interest, as well as a moral responsibility, to assist in controlling MDRTB in these 'hot spots'.

Antitubercular Agents↗

Addressing multidrug-resistant tuberculosis in penitentiary hospitals and in the general population of the former Soviet Union.

High rates of tuberculosis, including multidrug-resistant tuberculosis (MDR-TB), have been reported from the former Soviet Union. Our laboratory has supported operational studies in jails in Baku, Azerbaijan, and Mariinsk, Siberia. Combining the results from these two penal systems, the rates of MDR-TB among 'newly enrolled' and 'non-responding' cases were 24.6% and 92.1%, respectively. Restriction fragment length polymorphism (RFLP) studies strongly suggest transmission of MDR-TB between prisoners. In Mariinsk, the high rates of MDR-TB have been associated with failure rates of 23%-50% among smear-positive cases receiving fully-supervised standard short-course treatment. There are no coherent guidelines for TB control programmes confronted by high pre-existing levels of MDR-TB but who have only limited laboratory, clinical, pharmaceutical and financial resources. A 'DOTS plus' strategy has been advocated in which an established TB control programme is complemented by facilities to treat MDR-TB patients. However, the exact format of these programmes remains unresolved. Further research is required to describe the natural history of MDR-TB infection, to determine the failure rate of (and the additional resistance induced by) standard short-course treatment when MDR-TB is prevalent, to decide whether standardised or individualised second-line regimens can be employed, and to define the laboratory facilities required by a 'DOTS plus' programme.

Communicable Disease Control↗

Isolation of a novel mycobacterium from an adolescent with cervical lymphadenitis.

A slow-growing mycobacterium was isolated from a cervical lymph node of an adolescent male. This isolate produced small, smooth, scotochromogenic colonies after 6 weeks of incubation at 25 degrees C and 30 degrees C (but not at 37 degrees C or 43 degrees C). The results of 16S-rRNA gene sequencing and high-performance liquid chromatography suggest that this isolate belongs to a hitherto unrecognised pathogenic species.

Adolescent↗

Hepatitis C genotyping by direct sequencing of the product from the Roche AMPLICOR test: methodology and application to a South Australian population.

The Roche AMPLICOR RT-PCR amplifies a 244 nucleotide sequence within the 5' non coding region (5'NCR) of the viral genome and is a widely used commercial test for the qualitative determination of hepatitis C RNA from sera. This paper describes a routine procedure for the purification of the PCR product, and its use in automated DNA sequencing, for determining the genotype of hepatitis C virus (HCV) isolates. Direct sequencing of the purified product was possible for 86% of samples, whilst 14% required additional amplification using a nested PCR method in order to read the resulting electropherogram. This method of genotyping is considerably less expensive than currently available commercial kits, and is convenient for the increasing number of laboratories that have access to automated DNA sequencers. The highly conserved nature of the 5'NCR limited differentiation of types and subtypes to an extent comparable to commercial HCV typing methods. Using this method on available laboratory samples and on patients about to commence interferon therapy, we found a predominance of genotype 1 (59%) and 3a (31%). Analysis of data on the interferon patients showed the median length of time from first exposure to diagnosis to be significantly longer for patients with genotype 1 than genotype 3a.

Adult↗

New World cutaneous leishmaniasis imported into Australia.

A case of cutaneous leishmaniasis in a traveller from Belize, Central America is reported. Leishmaniasis presents rarely in Australia and delays in diagnosis and treatment often occur. A high index of suspicion in a patient who has returned from an endemic region is required. Subsequent confirmation of a diagnosis of cutaneous leishmaniasis is best achieved by demonstration of the organism on skin biopsy, aspiration or smear. The histology is variable and depends on geographic, parasite species and host factors. Speciation of New World disease as either Leishmania braziliensis or Leishmania mexicana is important to determine the risk of later development of mucosal disease, which normally only occurs with L. braziliensis infection, and for optimal treatment. Several different modes of treatment have been suggested, but antimonials, such as sodium stibogluconate, remain the treatment of choice in New World cutaneous leishmaniasis.

Adult↗

A community-based approach to the control of sexually transmitted diseases in the Northern Territory.

A program to control sexually transmitted diseases (STDs) was undertaken during a Men's Health Week in a remote Aboriginal community in Western Arnhem Land, Northern Territory. A total of 151 men aged 13 years and over who attended over a five-day period underwent a full physical examination, and first-void urine specimens were tested for the presence of leukocytes, chlamydia (by enzyme immunoassay antigen detection) and gonorrhoea (by culture and antigen detection). Blood was taken for syphilis serology from all patients and for human immunodeficiency virus (HIV) from patients with a proven STD or at the patient's request. Consent for testing was obtained from all participants. Patients with a positive urinary leukocyte test or symptoms were offered urethral swab investigations and treated empirically according to a set protocol. Patients with STDs detected by subsequent laboratory investigations were followed up and treated. The overall prevalence of one or more of syphilis, gonorrhoea or chlamydia was 17.4 per cent. No men presented with genitourinary symptoms and none was HIV-infected. In this population, STDs were an important cause of morbidity, and a community-based approach was adopted to identify infected persons. The use of urine for the detection of gonorrhoea and chlamydia was highly acceptable. Although not used in this study, polymerase chain reaction and ligase chain reaction technology will facilitate similar activities in the future.

Adolescent↗

Phenotypic and molecular characterization of three clinical isolates of Mycobacterium interjectum.

Introduction of molecular biology-based technology into an Australian mycobacterial reference laboratory has resulted in the identification of three isolates of Mycobacterium interjectum in the past 12 months. Conventional phenotypic methods failed to identify the species of these isolates, and high-performance liquid chromatography found that only one of the three isolates had a mycolic acid pattern similar to that of the type strain. In contrast, all three isolates were rapidly identified as M. interjectum by 16S rRNA gene sequence analysis. Two isolates were recovered from the lymph nodes of children with cervical lymphadenitis, confirming the pathogenicity of this organism. However, the third isolate was obtained from the sputum of an elderly male with chronic lung disease without evidence of clinical or radiological progression, suggesting that isolation of M. interjectum should not imply disease. With the increasing use of molecular biology-based technology in mycobacterial laboratories, M. interjectum may be recognized more frequently as a pathogen or commensal organism.

Aged↗

Pilot study of azithromycin in the treatment of genital donovanosis.

OBJECTIVES: To determine the effectiveness of azithromycin, an azalide antibiotic with long tissue half-life, in a pilot study of patients with genital donovanosis in the Northern Territory, Australia. DESIGN: Patients with histologically confirmed donovanosis were randomised to receive one of two open-label azithromycin dosage regimens: Regimen A--1.0 g once weekly for 4 weeks; or Regimen B--500 mg daily for 7 days. Patients were assessed at 6 weeks and classified as either "cured", "improved" or "failed". RESULTS: Seven patients received regimen A and 4 received regimen B. Six weeks after commencing treatment the genital ulcers of four patients receiving regimen A and one patient receiving regimen B had healed; the lesions of the other six patients (3 in each regimen) were "improved". No patient failed to respond and no significant adverse reaction was recognised. The eleven patients were reviewed after completing the six-week trial; all lesions had re-epithelialised without further antibiotic treatment, no relapses had occurred, the longest follow-up period being seven months. A further 17 patients with donovanosis who were unable to meet the entry criteria were also treated successfully with azithromycin during the study period. CONCLUSIONS: This is the first time that azithromycin has been shown to have clinical activity against donovanosis. Poor compliance with prolonged courses of antibiotics is one of the major barriers to control of the disease. Intermittent or short-course therapy, made possible by the long tissue half-life of the drug, could facilitate control of donovanosis in endemic populations if the high cost of medication can be addressed.

Adolescent↗