| 1. |
- Koivula, Tuija
(författare)
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Clinically important mycobacteria in Guinea-Bissau, West Africa : phenotypic and genetic diversity
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Tuberculosis (TB) is a major and still increasing health problem in West Africa. In Guinea-Bissau, TB has an estimated annual incidence of 1501100.000. Knowledge on infections caused by nontuberculous mycobacteria, such as Mycobacterium avium complex (MAC), is very limited in Africa, including Guinea-Bissau. M tuberculosis complex isolates (n=229) and MAC isolates (n=28) collected in Guinea-Bissau during 1989 to 1996, from sputum samples from approximately 1000 patients with clinical diagnosis of pulmonary TB, were analysed for phenotypical and genotypical characteristics. There was a high degree of heterogeneity in the M tuberculosis complex isolates in terms of biochemical properties as compared to what is normal in European isolates. Phenotypically, these isolates were assigned to one of five biovars, ranging within a spectrum of classical M. tuberculosis (biovar 5) to classical M. bovis (biovar 1). Genotypically, the strains could be divided into three groups (A-C), of which group A isolates are proposed to be imported and of European descent, while groups B and C isolates are unique and proposed to originate from West Africa (the Guinea-Bissau family of strains). A detailed genotypic analysis was carried out on 35 isolates from the Guinea-Bissau family. Based on the data obtained, and by comparing corresponding genes in mycobacteria outside the M. tuberculosis complex, it is proposed that the Guinea-Bissau family of strains is a unique branch of the M tuberculosis complex tree in between classical M. tuberculosis and classical M. bovis. Drug susceptibility testing demonstrated a low rate of resistance to drugs used for TB treatment in Guinea-Bissau. However, studies in vitro of thiacetazone showed that the minimum inhibitory concentration of this drug on M africanum subtype 11 strains (biovar 4) was significantly higher than that for other strains studied. It is concluded that in areas where M africanum subtype II is a prevalent cause of TB, thiacetazone should not be considered for treatment. M. bovis is known to lack the mtp40 gene. However, other investigators earlier reported two strains of M. bovis possessing the mtp40 gene. A detailed genotypic re-examination of these strains was performed showing that the two isolates, in fact, should be classified as M. africanum rather than M. bovis. This finding further strengthens the proposed evolutionary scenario of the M tuberculosis complex. The finding of MAC in sputum samples is one of the first reports of MAC in patients from Africa. The results demonstrate the importance of adequate laboratory diagnosis of mycobacteria. In geographic areas where MAC pulmonary infections are common, it is of significance to identify MAC, especially so in patients often incorrectly thought to suffer from drug-resistant TB. The MAC isolates were studied by several molecular methods. The highest discriminatory power was obtained with 16S rRNA sequencing. By this method most of the Guinea-Bissau strains were found to belong to the M. intracellulare branch of the phylogenetic tree of MAC. In summary, the phenotypic heterogeneity, and the genetic clustering revealed three major clusters allowing the identification of the new Guinea-Bissau family of M tuberculosis complex strains. This will contribute to a better understanding of the epidemiology of these organisms and also their evolution. The incidence of pulmonary MAC infections in patients in Guinea-Bissau, underlines the importance of correct laboratory diagnostic methods, not only for correct treatment, but also for epidemiological surveillance - frequently such MAC infections are incorrectly judged to be treatment failures caused by drug resistant TB complex organisms.
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| 2. |
- Norrgren, Hans, et al.
(författare)
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Higher mortality in HIV-2/HTLV-1 co-infected patients with pulmonary tuberculosis in Guinea-Bissau, West Africa, compared to HIV-2-positive HTLV-1-negative patients.
- 2010
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Ingår i: International Journal of Infectious Diseases. - : Elsevier BV. - 1878-3511 .- 1201-9712. ; May 4, s. 142-147
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate the effect of human T-lymphotropic virus type 1 (HTLV-1) on CD4 counts and mortality in tuberculosis (TB) patients with or without human immunodeficiency virus (HIV). METHODS: A prospective study on 280 hospitalized patients with pulmonary TB was performed in Guinea-Bissau, 1994-1997, including HIV, CD4 counts and clinical outcome. We compared the CD4 count levels at the time of inclusion between HIV-negative and HIV-positive patients, with or without HTLV-1. Mortality was determined while patients were on treatment for TB. RESULTS: Median CD4% was significantly higher in HIV-positive subjects co-infected with HTLV-1 compared to HTLV-1-negative patients. Two hundred thirty-three individuals were included in the analysis of mortality, and among HIV-negative subjects the mortality was 18.6/100 person-years . In HIV-2-positive HTLV-1-negative subjects the mortality was 39.5/100 person-years and in HIV-2/HTLV-1 co-infected patients it was 113.6/100 person-years (adjusted mortality rate ratio 4.7, 95% CI 1.5-14.4; p < 0.01). When all HIV-positive patients were analyzed together, corresponding mortality rates were 53.5/100 person-years and 104.8/100 person-years , respectively (not significant). CONCLUSIONS: HIV/HTLV-1 co-infected patients hospitalized for pulmonary TB had a high mortality and had significantly higher CD4% compared to only HIV-positive subjects. This may imply that HTLV-1 has an adverse effect on the immune system in HIV-infected subjects, independently of the CD4 count, that makes co-infected subjects more vulnerable to TB.
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| 3. |
- Norrgren, Hans, et al.
(författare)
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Increased prevalence of HTLV-1 in patients with pulmonary tuberculosis coinfected with HIV, but not in HIV-negative patients with tuberculosis
- 2008
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Ingår i: Journal of Acquired Immune Deficiency Syndromes. - Philadelphia, PA : Lippincott Williams & Wilkins. - 1525-4135 .- 1944-7884. ; 48:5, s. 607-610
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Tidskriftsartikel (refereegranskat)abstract
- Background: Few and inconclusive results have been presented regarding the influence of human T-lymphotropic virus 1 (HTLV-1) infection on the risk of acquiring tuberculosis (TB). Methods: In 1994-1997, we performed a prospective study on hospitalized adult patients with pulmonary TB in Guinea-Bissau and compared the clinical outcome in HIV-2 and HIV-negative patients. We determined the prevalence of HTLV-1 in all patients screened and diagnosed with TB in that study and compared the infection rate with a serosurvey of HTLV-1 in a population sample from a community-based study conducted at the same time and in the same city. Results: In the TB group, a total of 32 (11.4%) of 280 patients were positive for HTLV-1. This was significantly higher compared with the population-based group in which 74 (3.5%) of 2117 were HTLV-1 positive [crude odds ratio (OR) = 3.6; 95% confidence interval (CI) 2.2 to 5.6, P < 0.001]. However, in a logistic regression analysis controlling for age, gender, and HIV result, the difference was no longer significant (OR = 1.61; 95% CI 0.95 to 2.70, P = 0.074). In HIV-negative patients, no association was found between HTLV-1 and TB (OR = 1.18; 95% CI 0.48 to 2.89, P = 0.71), whereas a significant association was found in HIV-positive patients (OR = 2.41; 95% CI 1.26 to 4.61, P = 0.008). Conclusions: The immunosuppressive effect of HTLV-1 alone was not enough to increase the risk of TB in a highly endemic country, but HTLV-1 increased the risk of TB among HIV-infected individuals.
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| 4. |
- Sandegren, Linus, et al.
(författare)
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Genomic Stability over 9 Years of an Isoniazid Resistant Mycobacterium tuberculosis Outbreak Strain in Sweden
- 2011
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:1, s. e16647-
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Tidskriftsartikel (refereegranskat)abstract
- In molecular epidemiological studies of drug resistant Mycobacterium tuberculosis (TB) in Sweden a large outbreak of an isoniazid resistant strain was identified, involving 115 patients, mainly from the Horn of Africa. During the outbreak period, the genomic pattern of the outbreak strain has stayed virtually unchanged with regard to drug resistance, IS6110 restriction fragment length polymorphism and spoligotyping patterns. Here we present the complete genome sequence analyses of the index isolate and two isolates sampled nine years after the index case as well as experimental data on the virulence of this outbreak strain. Even though the strain has been present in the community for nine years and passaged between patients at least five times in-between the isolates, we only found four single nucleotide polymorphisms in one of the later isolates and a small (4 amino acids) deletion in the other compared to the index isolate. In contrast to many other evolutionarily successful outbreak lineages (e. g. the Beijing lineage) this outbreak strain appears to be genetically very stable yet evolutionarily successful in a low endemic country such as Sweden. These findings further illustrate that the rate of genomic variation in TB can be highly strain dependent, something that can have important implications for epidemiological studies as well as development of resistance.
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