[The new face of tuberculosis in Norway].
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Communicable Disease Control↗
Biomedical subjects
Morten Harboe
Publications and source records attributed to Morten Harboe.
[This is not our medical ethic].
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Ethics, Research↗
Characterization of Neisseria meningitidis isolates from recent outbreaks in Ethiopia and comparison with those recovered during the epidemic of 1988 to 1989.
The objectives of this study were to collect and characterize epidemic meningococcal isolates from Ethiopia from 2002 to 2003 and to compare them to 21 strains recovered during the previous large epidemic of 1988 to 1989. Ninety-five patients in all age groups with clinical signs of meningitis and a turbid cerebrospinal fluid (CSF) sample were included in the study of isolates from 2002 to 2003. Seventy-one patients (74.7%) were confirmed as having Neisseria meningitidis either by culture (n = 40) or by porA PCR (n = 31) of their CSF. The overall case fatality rate (CFR) was 11.6%; the N. meningitidis-specific CFR was 4.2%. All 40 strains were fully susceptible to all antibiotics tested except sulfonamide, were serotyped as A:4/21:P1.20,9, and belonged to sequence type 7 (ST-7). The strains from 1988 to 1989 were also equally susceptible and were characterized as A:4/21:P1.20,9, but they belonged to ST-5. Antigenic characterization of the strains revealed differences in the repertoire of lipooligosaccharides and Opa proteins between the old and the recent strains. PCR analysis of the nine lgt genes revealed the presence of the lgtAHFG genes in both old and recent strains; lgtB was present in only some of the strains, but no correlation with sequence type was observed. Further analysis showed that in addition to their pgm alleles, the Ethiopian ST-5 and ST-7 strains also differed in their tbpB, opa, fetA, and lgtA genes. The occurrence of new antigenic structures in strains sharing the same serogroup, PorA, and PorB may help explain the replacement of ST-5 by ST-7 in the African meningitis belt.
Adolescent↗
Challenges presented by nerve damage in leprosy.
The basis of nerve damage in leprosy is the unique tendency of Mycobacterium leprae to invade Schwann cells. alphaBeta-Dystroglycan on the basement membrane of Schwann cells binds to laminin alpha2, in turn binding to receptors on the M. leprae surface, comprising a histone-like protein and phenoglycolipid-1. When nerve damage during reversal reactions was found to be associated with an abrupt increase in delayed type hypersensitivity against M. leprae antigenic determinants released from Schwann cells, it suggested that the nerve is damaged as an innocent bystander during the immune response. This strongly influenced the introduction of therapy based on immunosuppression combined with continued anti-mycobacterial medication. Lysis of Schwann cells presenting M. leprae antigenic determinants by activated CD4+ T cells and interaction of M. leprae with Toll-like receptors on Schwann cells are additional mechanisms implicated in nerve damage. Persistence of M. leprae antigen in local lesions after regular multiple drug therapy (MDT) is an important risk factor for late reactions. In spite of significant advances in the provision of MDT globally, early diagnosis, together with effective treatment of the disease and associated nerve damage at initial presentation remains a major challenge for the health services. Reduced prevalence as a result of MDT should not be taken to indicate that the challenges of leprosy control are diminished as long as nerve damage is not controlled and new case detection rates are not declining.
Drug Therapy, Combination↗
T cell mediated immune responses in patients with tuberculous lymphadenitis from Butajira, southern Ethiopia.
The control of tuberculosis (TB) requires improved vaccines in addition to chemotherapy. It is essential to understand the immune response in tuberculosis to successfully evaluate potential vaccines. Current investigations have focused on immune responses in pulmonary forms. We studied the T-cell response of peripheral blood mononuclear cells (PBMC) from HIV-infected (n=8) and non-infected patients (n=19) with lymph node tuberculosis to PPD and short-term culture filtrates (ST-CF) of M. tuberculosis. PBMC from HIV-negative TB lymphadenitis patients proliferated in response to both antigens (p<0.001) and produced variably higher levels of IFN-gamma compared to healthy controls (p=0.02) (n=19) from the same area. Such responses were suppressed in HIV co-infected subjects. The results indicate that circulating PBMC in the apparently localized form of tuberculous lymphadenitis react to mycobacterial antigens in a similar pattern as those of patients with pulmonary disease.
Adult↗
Predicted molecular structure of the mammalian cell entry protein Mce1A of Mycobacterium tuberculosis.
The proposed role of the mammalian cell entry protein 1A (Mce1A) of Mycobacterium tuberculosis is to facilitate invasion of host cells. The structure of Mce1A was modelled on the basis of the crystal structure of Colicin N of Escherichia coli by fold prediction and threading. Mce1A, as the model predicts, is an alpha/beta protein consisting of two major (alpha and beta) domains, connected by a long alpha helix. The model further revealed that the protein contains 12 helices, 9 strands, and 1 turn. The final model of Mce1A was verified through the program VERIFY 3D and more than 90% of the residues were in the favourable region. A mouse monoclonal antibody, TB1-5 76C, is directed to an epitope within a 60-mer peptide that has been shown to promote uptake of bacteria in mammalian cells. We show here that the epitope could be narrowed down to a core of 4 amino acids, TPKD. Upstream flanking residues, KRR also contributed to binding. Mce2A does not promote uptake in mammalian cells and sequence comparison of Mce1A and Mce2A indicates that the epitope mediates uptake. The epitope was located at the surface of the Mce1A model at the distal beta strand-loop region in the beta domain. The localization of this epitope in the model confirms its potential role in promoting uptake of M. tuberculosis in host cells.
Algorithms↗
Diagnosis of tuberculous lymphadenitis in Butajira, rural Ethiopia.
Tuberculous lymphadenitis (TBLN) is a diagnostic challenge in sub-Saharan Africa, where there is a high rate of human immunodeficiency virus (HIV) infection. This study aimed to find ways to improve the diagnosis in Butajira, rural Ethiopia, where TBLN constitutes 40% of the total tuberculosis (TB) diagnosis. Among 147 clinically suspected cases, 107 (72.8%) were confirmed as TBLN by fine-needle aspiration (FNA) cytology and acid-fast bacillus (AFB) smear examination. Of the remaining 40 cases, denoted non-tuberculous lymphadenitis (NTBLN) after this smear examination, 37 (92.5%) showed a cytological pattern with neutrophil aggregates. The clinical manifestations were similar and cervical lymph nodes were the most affected in these 2 groups. 24 of the 107 TBLN cases (22.4%) and 9 (22.5%) of the other cases were seropositive for HIV infection (p > 0.5). FNA cytology combined with AFB smear examination is a good alternative to histology in rural Ethiopia where the expertise in taking biopsies is very limited. Polymerase chain reaction for Mycobacterium tuberculosis complex DNA was positive in 15 of 23 cases tested with NTBLN cytology, showing that an additional independent criterion for the presence of M. tuberculosis is needed for diagnosis in lymphadenitis cases of this kind. These findings could help to strengthen the diagnostic algorithm suggested by the National TB Control Program.
Adolescent↗
Improved cellular and humoral immune responses against Mycobacterium tuberculosis antigens after intramuscular DNA immunisation combined with muscle electroporation.
New delivery methods are needed to improve the efficiency of existing DNA vaccines. We have measured the immune response to Mycobacterium tuberculosis antigens following intramuscular DNA injection in combination with or without electroporation. Three to 6-fold increase in the number of antigen specific CD4(+) and CD8(+) T cells, measured by IFN-gamma-producing cells in an ELISPOT assay, was found in mice DNA injected and electroporated compared with non-electroporated mice. Similarly, 5 to 10-fold increase in antigen specific IgG1, IgG2a and IgG2b antibodies were found in an immunoglobulin subclass specific ELISA. A 100-fold reduction in DNA dose could be used without loss of efficiency when immunisation was combined with electroporation. A single injection of 1 microg of antigen 85b (ag85b) plasmid DNA was sufficient to elicit a higher and long lasting level of IgG2a antibodies against antigen 85B (Ag85B) compared to standard BCG vaccination. We conclude that DNA immunisation in combination with electroporation can significantly improve the immunogenicity of plasmid-based DNA vaccines.
Acyltransferases↗
Identification of the causative organism of tuberculous lymphadenitis in ethiopia by PCR.
UNLABELLED: Tuberculous lymphadenitis (TBLN) is a common form of extrapulmonary tuberculosis with multiple differential diagnoses. Demonstration of the etiologic agent by smear microscopy or culture of fine needle aspirate (FNA) specimens is often unsuccessful. FNA specimens from 40 patients presenting at a rural health center in South Ethiopia and diagnosed as positive for TBLN on the basis of clinical and cytological criteria were analyzed for mycobacterial DNA by PCR. Thirty (75%) had cervical lymphadenitis and 11 (27.5%) were seropositive for human immunodeficiency virus (HIV). Three primer sets were initially used to identify the causative agent at the genus (antigen 85 complex), complex (IS6110 insertion sequence), and species (pncA gene and allelic variation) levels. Among the forty TBLN cases, 35 (87.5%) were positive by PCR at the genus and complex levels. Based on PCR for detection of allelic variation at position 169, 24 (68.6%) of the 35 were positive for Mycobacterium tuberculosis and 6 (17.1%) were positive for M. bovis. These six were positive in additional PCR assays using the JB21-JB22 primer set, which is highly specific for M. bovis. Five (14.1%) showed amplification for both M. tuberculosis and M. bovis with the allele-specific primer set. Cooccurrence of pyrazinamide (PZA)-sensitive and -resistant M. tuberculosis in those five cases was indicated, since all were negative in assays with the JB21-JB22 primer set. This feature was seen in 3 of 11 HIV-positive and 2 of 29 HIV-negative individuals (P < 0.001). CONCLUSION: among 35 PCR-positive cases of TBLN from southern Ethiopia, 29 (82.9%) were caused by M. tuberculosis and six (17.1%) were caused by M. bovis.
Biopsy, Needle↗