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Biomedical subjects

Gunnar Bjune

Publications and source records attributed to Gunnar Bjune.

At least 19 recordsLinked to original sources

[Tuberculosis vaccines].

Even though the BCG vaccine is one of the most used vaccines in the world, tuberculosis is still a major problem worldwide. Research aimed at developing new vaccines against tuberculosis has become more goal-directed during the last 10-15 years, and there are now several vaccine candidates in clinical study phases I and II, that should be in phase III in 2010. It will then still take several years before we know whether a new vaccine will reduce the occurrence of tuberculosis. There are several promising vaccine candidates, but there is uncertainty whether they will be successful in reducing tuberculosis, as we do not have sufficient knowledge about protective immunity in tuberculosis. Today's vaccine candidates have been developed to protect against a few laboratory strains of the bacteria and will not protect against all strains. Estimations show that an effective vaccine against latent tuberculosis will give a rapid and considerable reduction in tuberculosis. The current vaccine candidates are however developed to protect against primary tuberculosis and not against reactivated latent tuberculosis. It is important to ensure an optimal experimental basis for new tuberculosis vaccines and to compare them so the best can be selected.

Adult↗

Patient and health care system delays in the start of tuberculosis treatment in Norway.

BACKGROUND: Delay in start of tuberculosis (TB) treatment has an impact at both the individual level, by increasing the risk of morbidity and mortality, and at the community level, by increasing the risk of transmission. The aims of this study were to assess the delays in the start of treatment for TB patients in Oslo/Akershus region, Norway and to analyze risk factors for the delays. METHODS: This study was based on information from the National TB Registry, clinical case notes from hospitals and referral case notes from primary health care providers. Delays were divided into patient, health care system and total delays. The association with sex, birthplace, site of the disease and age group was analyzed by multiple linear regression. RESULTS: Among the 83 TB patients included in this study, 71 (86%) were born abroad. The median patient, health care system and total delays were 28, 33 and 63 days respectively, with a range of 1-434 days. In unadjusted analysis, patient delay and health care system delay did not vary significantly between men and women, according to birthplace or age group. Patients with extra-pulmonary TB had a significantly longer patient, health care system and total delay compared to patients with pulmonary TB. Median total delay was 81 and 56 days in the two groups of TB patients respectively. The health care system delay exceeded the patient delay for those born in Norway. The age group 60+ years had significantly shorter patient delay than the reference group aged 15-29 years when adjusted for multiple covariates. Also, in the multivariate analysis patients born in Norway had significantly longer health care system delay than patients born abroad. CONCLUSION: A high proportion of patients had total delays in start of TB treatment exceeding two months. This study emphasizes the need of awareness of TB in the general population and among health personnel. Extra-pulmonary TB should be considered as a differential diagnosis in unresolved cases, especially for immigrants from high TB prevalence countries.

Adolescent↗

Assessment of routine surveillance data as a tool to investigate measles outbreaks in Mozambique.

BACKGROUND: Measles remains a major public health problem in Mozambique despite significant efforts to control the disease. Currently, health authorities base their outbreak control on data from the routine surveillance system while vaccine coverage and efficacy are calculated based on mathematical projections of the target population. The aim of this work was to assess the quality of the measles reporting system during two outbreaks that occurred in Maputo City (1998) and in Manica Province (2002). METHODS: Retrospectively, we collected data from the routine surveillance system, i.e. register books at health facilities and weekly provincial and national epidemiological reports. To test whether the provinces registered an outbreak, the distribution of measles cases was compared to an endemic level established based on cases reported in previous years. RESULTS: There was a significant under-notification of measles cases from the health facilities to the province and national level. Register books, the primary sources of information for the measles surveillance system, were found to be incomplete for two main variables: "age" and "vaccination status". CONCLUSION: The Mozambican surveillance system is based on poor quality records, receives the notification of only a fraction of the total number of measles in the country and may result in failures do detect epidemics. The measles reporting system does not provide the data needed by Expanded Program on Immunisation managers to make evidence-based decisions, nor does it allow in-depth analysis to monitor measles epidemiology in the country. The progress of Mozambique to the next stage of measles elimination will require an improvement of the routine surveillance system and a stronger Health Information System.

Adolescent↗

Immunization coverage in Mozambique: from concepts to decision-making.

Immunization is an effective strategy to reduce morbidity and mortality among children. This recognition has led many countries to concentrate efforts in establishing desirable achievements in the form of immunization coverage figures. However, less focus has been placed on effort made by different countries to attain high immunization coverage. During August 2002, 14 district health directors in a remote province of Mozambique (Niassa) were interviewed. The objective was to ascertain the construction of immunization coverage and how they implement the desired program strategies in order to improve the health status of the region. We found that most managers regarded the immunization coverage as data and thus high coverage as an end in itself, rather than as a reflection of the reality. We also found that there are uncertainties in population data which makes it difficult to plan activities bellow the level of a district. We argue further that the innovative distinction between the views proposed on the immunization coverage, provided us with an insight of the different challenges that district health directors face as leaders of the district health management team in Niassa. Clues on the implications of certain views of immunization coverage for policy and local decision-making in the national and global pursuit of immunization targets are provided.

Attitude of Health Personnel↗

Heterogeneity of Mycobacterium tuberculosis isolates in Sunamganj District, Bangladesh.

A total of 111 Mycobacterium tuberculosis isolates from new pulmonary tuberculosis patients, living in the rural Sunamganj district in northern Bangladesh were characterized with IS6110 restriction fragment length polymorphism analyses and spoligotyping. Only 3 of the isolates belonged to the W-Beijing genotype of M. tuberculosis. A high degree of diversity indicated that the spread of M. tuberculosis, in this rural area, was not caused by closely related genotypes. The tuberculosis cases in the current study were less likely to represent recent transmission than what is commonly observed in urban parts of south-east Asia. It was indicated that the tuberculosis cases of this isolated area, of a high-incidence country, represented those of an established epidemic, not yet influenced by recently disseminated strains.

Bangladesh↗

Diagnostic and treatment delay among pulmonary tuberculosis patients in Ethiopia: a cross sectional study.

BACKGROUND: Delayed diagnosis and treatment of tuberculosis (TB) results in severe disease and a higher mortality. It also leads to an increased period of infectivity in the community. The objective of this study was to determine the length of delays, and analyze the factors affecting the delay from onset of symptoms of pulmonary tuberculosis (PTB) until the commencement of treatment. METHODS: In randomly selected TB management units (TBMUs), i.e. government health institutions which have diagnosing and treatment facilities for TB in Amhara Region, we conducted a cross sectional study from September 1-December 31/2003. Delay was analyzed from two perspectives, 1. Period between onset of TB symptoms to first visit to any health provider (health seeking period), and from the first health provider visit to initiation of treatment (health providers' delay), and 2. Period between onset of TB symptoms to first visit to a medical provider (patients' delay), and from this visit to commencement of anti-TB treatment (health systems' delay). Patients were interviewed on the same date of diagnosis using a semi-structured questionnaire. Logistics regression analysis was applied to analyze the risk factors of delays. RESULTS: A total of 384 new smear positive PTB patients participated in the study. The median total delay was 80 days. The median health-seeking period and health providers' delays were 15 and 61 days, respectively. Conversely, the median patients' and health systems' delays were 30 and 21 days, respectively. Taking medical providers as a reference point, we found that forty eight percent of the subjects delayed for more than one month. Patients' delays were strongly associated with first visit to non-formal health providers and self treatment (P < 0.0001). Prior attendance to a health post/clinic was associated with increased health systems' delay (p < 0.0001). CONCLUSION: Delay in the diagnosis and treatment of PTB is unacceptably high in Amhara region. Health providers' and health systems' delays represent the major portion of the total delay. Accessing a simple and rapid diagnostic test for TB at the lowest level of health care facility and encouraging a dialogue among all health providers are imperative interventions.

Adolescent↗

Epidemic of tuberculosis in the former Soviet Union: social and biological reasons.

The tuberculosis epidemic was evidenced in the states of the former Soviet Union at the end of the 20th century. The increase of epidemiological indicators for tuberculosis was accelerated by socio-economic changes in the society. Laboratory analysis also revealed new biological properties of the Mycobacterium tuberculosis isolates in the region, in particular the high level of resistance to antibiotics. Tuberculosis in Russia and the other newly independent states has been caused by M. tuberculosis strains of the W-Beijing family in recent years. These bacteria have rapidly developed resistance to anti-tuberculosis drugs, as a result of prolonged exposure of the patients to inappropriate treatment. The epidemic of drug-resistant tuberculosis caused by the W-Beijing strains represents an important threat to the health of the populations in the newly independent states. It may also adversely affect the global trends in tuberculosis, as there is a clear risk that these drug-resistant strains can spread to other communities outside the former Soviet Union.

Antibiotics, Antitubercular↗

Assessing immunization data quality from routine reports in Mozambique.

BACKGROUND: Worldwide immunization coverage shows an increase in the past years but the validity of the official reports for measuring change over time has been questioned. Facing this problem, donor supported initiatives like the Global Alliance for Vaccine and Immunizations, have been putting a lot of effort into assessing the quality of data used, since accurate immunization information is essential for the Expanded Program on Immunization managers to track and improve program performance. The present article, discusses the practices on record keeping, reporting and the support mechanism to ensure data quality in Mozambique. METHODS: A process evaluation study was carried out in Mozambique in one district (Cuamba) in Niassa Province, between January and March 2003. The study was based on semi-structured interviews, participant observation and review of the data collection materials. RESULTS: Differences were found for all vaccine types when comparing facility reports with the tally sheets. The same applies when comparing facility reports with district reports. The study also showed that a routine practice during supervision visits was data quality assessment for the outpatient services but none related to data consistency between the tally sheets and the facility report. For the Expanded Program on Immunization, supervisors concentrated more on the consistency checks between data in the facility reports and the number of vaccines received during the same period. Meetings were based on criticism, for example, why health workers did not reach the target. Nothing in terms of data quality was addressed nor validation rules. CONCLUSION: In this paper we have argued that the quality of data, and consequently of the information system, must be seen in a broader perspective not focusing only on technicalities (data collection tools and the reporting system) but also on support mechanisms. Implications of a poor data quality system will be reflected in the efficiency of health services facing increased demands, with stagnant or decreasing resources.

Child↗

Treatment outcome of new culture positive pulmonary tuberculosis in Norway.

BACKGROUND: The key elements in tuberculosis (TB) control are to cure the individual patient, interrupt transmission of TB to others and prevent the tubercle bacilli from becoming drug resistant. Incomplete treatment may result in excretion of bacteria that may also acquire drug resistance and cause increased morbidity and mortality. Treatment outcome results serves as a tool to control the quality of TB treatment provided by the health care system. The aims of this study were to evaluate the treatment outcome for new cases of culture positive pulmonary TB registered in Norway during the period 1996-2002 and to identify factors associated with non-successful treatment. METHODS: This was a register-based cohort study. Treatment outcome was assessed according to sex, birthplace, age group, isoniazid (INH) susceptibility, mode of detection and treatment periods (1996-1997, 1998-1999 and 2000-2002). Logistic regression was also used to estimate the odds ratio for treatment success vs. non-success with 95% confidence interval (CI), taking the above variables into account. RESULTS: Among the 655 patients included, the total treatment success rate was 83% (95% CI 80%-86%). The success rates for those born in Norway and abroad were 79% (95% CI 74%-84%) and 86% (95% CI 83%-89%) respectively. There was no difference in success rates by sex and treatment periods. Twenty-two patients (3%) defaulted treatment, 58 (9%) died and 26 (4%) transferred out. The default rate was higher among foreign-born and male patients, whereas almost all who died were born in Norway. The majority of the transferred out group left the country, but seven were expelled from the country. In the multivariate analysis, only high age and initial INH resistance remained as significant risk factors for non-successful treatment. CONCLUSION: Although the TB treatment success rate in Norway has increased compared to previous studies and although it has reached a reasonable target for treatment outcome in low-incidence countries, the total success rate for 1996-2002 was still slightly below the WHO target of success rate of 85%. Early diagnosis of TB in elderly patients to reduce the death rate, abstaining from expulsion of patients on treatment and further measures to prevent default could improve the success rate further.

Adolescent↗

Impact of drug resistance on fitness of Mycobacterium tuberculosis strains of the W-Beijing genotype.

Mycobacterium tuberculosis strains of the W-Beijing genotype became a common cause of tuberculosis during the past years and they are often associated with drug resistance. The biological factors facilitating the selection and wide dissemination of these strains are not known. To determine how acquisition of drug resistance affected growth of strains of the W-Beijing genotype, the growth of 55 M. tuberculosis isolates were studied using the BBL MGIT Mycobacteria Growth Indicator Tube and the BACTEC MGIT 960 System. Susceptible strains of non-Beijing genotypes were found to be the most fit strains. Drug-resistant strains of non-Beijing genotypes were more likely to grow slower than susceptible strains (P=0.001). Drug-resistant strains of the W-Beijing genotype had two tendencies of growth: some of them showed reduced growth compared to susceptible strains, while others did not show loss of fitness measured as growth.

Antitubercular Agents↗

Molecular epidemiology and drug resistance of Mycobacterium tuberculosis isolates in the Archangel prison in Russia: predominance of the W-Beijing clone family.

Prisons play a significant role in the epidemiology of drug-resistant tuberculosis. A total of 114 Mycobacterium tuberculosis isolates recovered from patients in the Archangel prison (Archangel, Russia) in 2001 were studied using restriction fragment-length polymorphism analysis and spoligotyping. Drug susceptibility was analyzed by the radiometric broth method (BACTEC; Becton Dickinson Diagnostic Systems). According to genotyping studies, 87 (76.3%) of the isolates belonged to the W-Beijing family. Nearly all (96.6%) W-Beijing isolates were part of a cluster, whereas only 25.9% of the other isolates were clustered (P<.001). The largest cluster comprised 43 patients. Multidrug resistance was high among new (34.0%) and previously treated (55.0%) cases. Resistance to ethambutol (OR, 3.4; 95% CI, 1.0-12.7; P=.03) and streptomycin (OR, 4.2; 95% CI, 1.5-11.6; P=.001) was significantly associated with infection with W-Beijing isolates. Tuberculosis due to drug-resistant W-Beijing isolates is a major problem in the Archangel prison.

Adolescent↗

Reproductive health perceptions, beliefs and sexual risk-taking among youth in Addis Ababa, Ethiopia.

Appropriate knowledge and beliefs about sexuality and necessary life skills do not often precede sexual behaviours among young people. This study outlines a profile of sexual risk factors and the underlying sexual and reproductive health perception and beliefs among youth (aged 15-24 years) in Addis Ababa, Ethiopia. Five hundred and sixty-one youth residing in two of the six zones of Addis Ababa filled a self-administered questionnaire. Three outcome variables: history of sexual activity in the past, use of condom during recent sexual intercourse and use of alcohol, were used to construct a pyramid of sexual risk categories. Being a female, age group of 20-24 years and out-of-school significantly increased the likelihood of belonging to the most vulnerable category. Although young people were heterogeneous in their sexual risk-taking, they were equally uninformed on reproductive health matters related to puberty and sexuality. Their respective beliefs also tended to be flexible and unstable to consistently predict their behaviour. Possible reasons for such heterogeneity and its practical implications in sex education strategies are discussed.

Adolescent↗

Mycobacterium tuberculosis mammalian cell entry operon (mce) homologs in Mycobacterium other than tuberculosis (MOTT).

The cloned mammalian cell entry gene mce1a from Mycobacterium tuberculosis confers to non-pathogenic Escherichia coli the ability to invade and survive inside macrophages and HeLa cells. The aim of this work was to search for and characterize homologs of the four M. tuberculosis mammalian cell entry operons (mce1, mce2, mce3 and mce4) in mycobacteria other than tuberculosis (MOTT). The dot-blot and polymerase chain reaction (PCR) experiments performed on 24 clinical isolates representing 20 different mycobacterial species indicated that the mce operons were widely distributed throughout the genus Mycobacterium. BLAST search results showed the presence of mce1, mce2 and mce4 homologs in Mycobacterium bovis, Mycobacterium avium and Mycobacterium smegmatis. A homologous region for the mce3 operon was also found in M. avium and M. smegmatis. DNA and protein alignments were done to compare the M. tuberculosis mce operons and the deduced M. bovis, M. avium, and M. smegmatis homologs. The deduced proteins of M. bovis mce1, mce2 and mce4 operons had 99.6-100% homology with the respective M. tuberculosis mce proteins (MTmce). The similarity between M. avium mce proteins and the individual M. tuberculosis homologs ranged from 56.2 to 85.5%. The alignment results between M. smegmatis mce proteins and the respective MTmce proteins ranged from 58.5% to 68.5%. Primer sets were designed from the M. tuberculosis mce4a gene for amplification of 379-bp fragments. Amplification was successful in 14 strains representing 11 different mycobacterial species. The PCR fragments were sequenced from 10 strains representing eight species. Alignment of the sequenced PCR products showed that mce4a homologs are highly conserved in the genus Mycobacterium. In conclusions, the four mce operons in different mycobacterial species are generally organized in the same manner. The phylogenetic tree comparing the different mce operons showed that the mce1 operon was closely related to the mce2 operon and mce3 diverged from the other operons. The wide distribution of the mce operons in pathogenic and non-pathogenic mycobacteria implicates that the presence of these putative virulence genes is not an indicator for the pathogenicity of the bacilli. Instead, the pathogenicity of these factors might be determined by their expression.

Amino Acid Sequence↗

Clinical and radiological features in relation to urinary excretion of lipoarabinomannan in Ethiopian tuberculosis patients.

We have previously reported on the diagnostic potential of urinary lipoarabinomannan (LAM) detection in active tuberculosis (TB). In this study, we identified clinical and radiological parameters that were significantly associated with urine LAM positivity in a clinical sample of 931 patients attending a TB control center in Addis Ababa, Ethiopa. These parameters were attributed weights and used in a diagnostic score (DS) system. Using urinary LAM as a reference, this DS system showed a sensitivity of 65.4% and a specificity of 82.9%. The positive and negative predictive values were 56.8% and 87.4%, respectively. HIV or other coinfections or deficiencies may have blurred the clinical manifestations of pulmonary TB (PTB) and thereby contributed to the relatively high number of false-positive DS results obtained. Although additional markers may be required to improve the sensitivity of the DS system, the relatively high specificity of this simple approach may be of some practical use in the field. Thus, in PTB-suspected, DS-negative cases, the likelihood of ongoing PTB is < 20%.

Biomarkers↗

Circulating antibodies to lipoarabinomannan in relation to sputum microscopy, clinical features and urinary anti-lipoarabinomannan detection in pulmonary tuberculosis.

An enzyme-linked immunosorbent assay (ELISA)-based investigation of anti-lipoarabinomannan (LAM) antibody levels in the sera of patients with acid-fast bacilli (AFB)-positive pulmonary tuberculosis (PTB), AFB-negative PTB and non-TB respiratory tract symptoms was conducted. The anti-LAM results were further evaluated using urine LAM detection and a clinical diagnostic score (DS) system as references. Using sputum AFB as a reference, positive anti-LAM was found in 66.9% of 139 AFB-positive PTB, 34.4% of 61 AFB-negative PTB and 23.5% of 800 non-TB patients and in 8% of 50 healthy individuals. The positive and negative predictive values were 48.7% and 87.4%, respectively. Using the DS as a reference, the sensitivity and specificity were 50.5% and 78.3%, respectively, whereas 45.8% of urine LAM positives and 77.9% of urine LAM negatives were correctly identified by the anti-LAM ELISA. In TB endemic areas a negative anti-LAM could be of practical value, particularly when other indicators of PTB are negative. Using any of these methods as a reference, a positive anti-LAM would mislead in about one-quarter of cases. Had all the 3 methods been combined and at least 2 positive tests sufficed, 90.6% of AFB-positive PTB, 52.5% of AFB-negative PTB and 94.9% of non-TB patients would have been correctly diagnosed. Apart from the possible impact of HIV, the low accuracy of the current assay could be due to intravascular formation of LAM-anti-LAM complexes, latent TB or environmental mycobacterial infections.

Adult↗

Prevalence of gonococcal and chlamydial infections and sexual risk behavior among youth in Addis Ababa, Ethiopia.

BACKGROUND: No community-based study on the magnitude of sexually transmitted diseases (STDs) has ever been conducted among young people in Ethiopia. GOAL: To assess the magnitude of Chlamydia trachomatis and Neisseria gonorrhoeae infections and status of sexual risk behavior among youths (15-24 years old) in Addis Ababa, Ethiopia. STUDY DESIGN: Youths in or out of school residing in two (of the six) administrative zones in Addis Ababa served as the study population. Participants filled out a self-administered questionnaire related to sexuality and its sociocultural determinants. First-void urine (FVU) was analyzed for gonorrhea and chlamydial infection by polymerase chain reaction (PCR). RESULTS: A total of 561 youths took part in the study. Urine PCR was performed for 522 of them. Nine subjects (1.7%) were found to have and N gonorrhoeae and C trachomatis infections. There were five cases (1.0%) involving each agent. Double infection was noted in one female subject. All but one of the infections were detected among the out-of-school youths (chi-square = 4.5; < 0.05). None of these subjects complained of symptoms suggestive of an active STD. One-third (188/561) reported having had sexual intercourse. The prevalence among sexually active youths was thus 4.8% (9/188) for both infections combined (2.7% for each agent). While 7/52 (13.5%) of the sexually active females were found to also have STDs, only 2/136 (1.5%) of the males had an STD (chi-square = 8.0; < 0.01). Report of sexual activity was significantly associated with being male, an age of >/=20 years, out-of-school status, and report of alcohol/khat (amphetamine-like substance) consumption. Females reported less condom use, whether they were in or out of school and independent of age. CONCLUSIONS: Out-of-school youths, especially females, took more sexual risk and were exceedingly susceptible to STDs. This calls for alternative group-targeted strategies for sex education, disease prevention, and STD screening and management.

Adolescent↗

Expression of the mceA, esat-6 and hspX genes in Mycobacterium tuberculosis and their responses to aerobic conditions and to restricted oxygen supply.

The expression of six of the mammalian cell-entry (mce1a-mce1f) genes of the mce1 operon of Mycobacterium tuberculosis has been described previously. In this study, data are presented for the expression of other mammalian cell-entry homologues (mce-2a, mce-3a and mce-4a) at the RNA level, as determined by RT-PCR. The stress responses of these genes and of other immunologically important antigens are also characterized with respect to the introduction of oxygen depletion. Analysis of the expression of the mceA genes in relation to oxygen depletion revealed that they were expressed differentially. The RT-PCR results showed that mce-1a, mce-2a, hspX (encoding the alpha-crystallin antigen Acr) and esat-6 (encoding the early secretory antigenic target-6) were expressed throughout the cultivation period, whereas the expression of mce-3a and mce-4a was downregulated in the later stages of cultivation. This study gives new insights into the expression profiles of the different mce operons and the hspX and esat-6 genes in an in vitro model of dormant-like bacilli. Identification of the genes that are differentially expressed under aerobic conditions and under oxygen-limited conditions contributes to our understanding of the bacilli involved in latent tuberculosis.

Aerobiosis↗

Spread of drug-resistant Mycobacterium tuberculosis strains of the Beijing genotype in the Archangel Oblast, Russia.

A collection of 119 strains of Mycobacterium tuberculosis isolated from patients with pulmonary tuberculosis in the Archangel Oblast, Russia, in 1998 and 1999 were studied by using restriction fragment length polymorphism (RFLP) analysis with the IS6110 probe and spoligotyping. Resistance of the strains to antituberculosis drugs was analyzed by the BACTEC method, and mutations associated with rifampin resistance were detected by using the Inno-LiPA Rif. TB test. RFLP analysis and spoligotyping demonstrated that 53 (44.5%) of the strains belonged to the Beijing genotype. These strains showed a significantly higher rate of resistance than M. tuberculosis strains of other genotypes circulating in the region. In particular, 43.4% of the strains of the Beijing genotype were multidrug resistant; in contrast, only 10.6% of the other strains were. Of the strains of the Beijing genotype, 92.5% were part of a cluster, while only 33.3% of the remaining strains were clustered. Analysis of the medical records of the patients demonstrated that individuals infected with a strain of the Beijing genotype were significantly more likely to be alcohol abusers and to have chronic obstructive pulmonary disease prior to the tuberculosis diagnosis. Multivariate analysis showed that both variables were independently associated with infection by strains belonging to the Beijing genotype. Our study demonstrated that strains of the Beijing genotype are an important cause of tuberculosis in the Archangel Oblast and that dissemination of these strains is associated with the high incidence of drug resistance.

Adult↗