Biomedical subjects

Albert I Ko

Publications and source records attributed to Albert I Ko.

11 recordsLinked to original sources

PubMed2007

High serum nitric oxide levels in patients with severe leptospirosis.

Leptospirosis is a globally distributed zoonosis of major public health importance and is associated with severe disease manifestations such as acute renal failure and pulmonary haemorrhage syndrome. However, the extent to which the pathogenesis of leptospirosis mimics sepsis caused by Gram-negative bacteria remains unknown. The aim of this study was to evaluate serum levels of nitric oxide (NO) in patients diagnosed with severe leptospirosis. Sera from 35 confirmed cases of severe leptospirosis and 13 healthy subjects were analysed. Patients with severe leptospirosis had significantly higher NO levels compared to healthy individuals (30.82+/-10.90 microM versus 3.86+/-1.34 microM, P < 0.001), indicating that this immune mediator plays a role in the underlying systemic inflammatory response.

Adolescent↗

PubMed2006

Isolation of Leptospira noguchii from sheep.

The main goal of this study was to obtain new isolates of Leptospira spp. from sheep. A total of 10 kidney samples and 44 blood samples were collected from sheep slaughtered in Pelotas, Southern Brazil. One isolate was obtained which was identified by 16S rRNA gene sequencing and serogrouping to be Leptospira noguchii serogroup Autumnalis. Microscopic agglutination test (MAT) evaluation revealed that 4.5% of the sheep sera reacted against the Autumnalis serogroup. This is the first report of isolation of L. noguchii from sheep. Together these findings indicate that L. noguchii infections may be a potentially important veterinary problem in this domestic animal species.

Agglutination Tests↗

PubMed2005

Leptospirosis.

PURPOSE OF REVIEW: Leptospirosis, a spirochaetal zoonotic disease, has been recognized as an important emerging infectious disease in the last 10 years. This review addresses the issues in the epidemiology, diagnosis and clinical management which confront public health responses, and highlights the progress made towards understanding the Leptospira genome, biology and pathogenesis. RECENT FINDINGS: Leptospirosis has spread from its traditional rural base to become the cause of epidemics in poor urban slum communities in developing countries. Mortality from severe disease forms, Weil's disease and severe pulmonary haemorrhage syndrome, is high (>10% and >50%, respectively) even when optimal treatment is provided. Moreover, the overall disease burden is underestimated, since leptospirosis is a significant cause of undifferentiated fever and frequently not recognized. Barriers to addressing this problem have been the lack of an adequate diagnostic test and effective control measures. China and Brazil, countries in which leptospirosis is a major health problem, have completed the sequence of the Leptospira interrogans genome. Together with new genetic tools and proteomics, new insights have been made into the biology of Leptospira and the mechanisms used to adapt to host and external environments. Surface-exposed proteins and putative virulence determinants have been identified which may serve as sub-unit vaccine candidates. SUMMARY: Major progress has been made in the basic research of leptospirosis. Future challenges will be to translate these advances into public health measures for developing countries. Yet the most effective responses may be interventions that directly address the determinants of poverty, such as poor sanitation, which are often responsible for transmission.

Genome, Bacterial↗

PubMed2005

Surfaceome of Leptospira spp.

The identification of the subset of outer membrane proteins exposed on the surface of a bacterial cell (the surfaceome) is critical to understanding the interactions of bacteria with their environments and greatly narrows the search for protective antigens of extracellular pathogens. The surfaceome of Leptospira was investigated by biotin labeling of viable leptospires, affinity capture of the biotinylated proteins, two-dimensional gel electrophoresis, and mass spectrometry (MS). The leptospiral surfaceome was found to be predominantly made up of a small number of already characterized proteins, being in order of relative abundance on the cell surface: LipL32 > LipL21 > LipL41. Of these proteins, only LipL32 had not been previously identified as surface exposed. LipL32 surface exposure was subsequently verified by three independent approaches: surface immunofluorescence, whole-cell enzyme-linked immunosorbent assay (ELISA), and immunoelectron microscopy. Three other proteins, Q8F8Q0 (a putative transmembrane outer membrane protein) and two proteins of 20 kDa and 55 kDa that could not be identified by MS, one of which demonstrated a high degree of labeling potentially representing an additional, as-yet-uncharacterized, surface-exposed protein. Minor labeling of p31(LipL45), GroEL, and FlaB1 was also observed. Expression of the surfaceome constituents remained unchanged under a range of conditions investigated, including temperature and the presence of serum or urine. Immunization of mice with affinity-captured surface components stimulated the production of antibodies that bound surface proteins from heterologous leptospiral strains. The surfaceomics approach is particularly amenable to protein expression profiling using small amounts of sample (<10(7) cells) offering the potential to analyze bacterial surface expression during infection.

Animals↗

PubMed2003

Pathogenic Leptospira species express surface-exposed proteins belonging to the bacterial immunoglobulin superfamily.

Proteins with bacterial immunoglobulin-like (Big) domains, such as the Yersinia pseudotuberculosis invasin and Escherichia coli intimin, are surface-expressed proteins that mediate host mammalian cell invasion or attachment. Here, we report the identification and characterization of a new family of Big domain proteins, referred to as Lig (leptospiral Ig-like) proteins, in pathogenic Leptospira. Screening of L. interrogans and L. kirschneri expression libraries with sera from leptospirosis patients identified 13 lambda phage clones that encode tandem repeats of the 90 amino acid Big domain. Two lig genes, designated ligA and ligB, and one pseudogene, ligC, were identified. The ligA and ligB genes encode amino-terminal lipoprotein signal peptides followed by 10 or 11 Big domain repeats and, in the case of ligB, a unique carboxy-terminal non-repeat domain. The organization of ligC is similar to that of ligB but contains mutations that disrupt the reading frame. The lig sequences are present in pathogenic but not saprophytic Leptospira species. LigA and LigB are expressed by a variety of virulent leptospiral strains. Loss of Lig protein and RNA transcript expression is correlated with the observed loss of virulence during culture attenuation of pathogenic strains. High-pressure freeze substitution followed by immunocytochemical electron microscopy confirmed that the Lig proteins were localized to the bacterial surface. Immunoblot studies with patient sera found that the Lig proteins are a major antigen recognized during the acute host infection. These observations demonstrate that the Lig proteins are a newly identified surface protein of pathogenic Leptospira, which by analogy to other bacterial immunoglobulin superfamily virulence factors, may play a role in host cell attachment and invasion during leptospiral pathogenesis.

Amino Acid Sequence↗

PubMed2002

Prevention of Haemophilus influenzae type b (Hib) meningitis and emergence of serotype replacement with type a strains after introduction of Hib immunization in Brazil.

Surveillance for Haemophilus influenzae meningitis cases was performed in Salvador, Brazil, before and after introduction of H. influenzae type b (Hib) immunization. The incidence of Hib meningitis decreased 69% during the 1-year period after initiation of Hib immunization (from 2.62 to 0.81 cases/100,000 person-years; P<.001). In contrast, the incidence for H. influenzae type a meningitis increased 8-fold (from 0.02 to 0.16 cases/100,000 person-years; P=.008). Pulsed-field gel electrophoretic analysis demonstrated that H. influenzae type a isolates belonged to 2 clonally related groups, both of which were found before Hib immunization commenced. Therefore, Hib immunization contributed to an increased risk for H. influenzae type a meningitis through selection of circulating H. influenzae type a clones. The risk attributable to serotype replacement is small in comparison to the large reduction in Hib meningitis due to immunization. However, these findings highlight the need to maintain surveillance as the use of conjugate vaccines expands worldwide.

Bacterial Capsules↗

PubMed2002

Disseminated leishmaniasis: a new and emerging form of leishmaniasis observed in northeastern Brazil.

During the past decade, there has been an increase in the number of patients with disseminated leishmaniasis (DL), which is characterized by a large number of acneiform and papular skin lesions, with very few or no parasites in the skin tissue. The present report describes 42 cases of DL identified between 1992 and 1998 in an area where Leishmania braziliensis transmission is endemic; 8 of the patients were prospectively diagnosed. In a contrast to localized cutaneous leishmaniasis (LCL), acquisition of DL was associated with age >19 years (P<.05), male sex (P<.05), and agricultural occupation (P<.001). Patients with DL presented with 10-300 lesions that were a mixture of acneiform, papular, nodular, and ulcerated types. Twelve (29%) of 42 patients had mucosal involvement. Patients with DL had lower levels of interferon-gamma (P<.05) and tumor necrosis factor-alpha (P<.05) production, compared with patients with LCL. DL is an emerging clinical distinct form of leishmaniasis associated with agricultural activities and host immunological response.

Adult↗

PubMed2002

Antimicrobial resistance in Haemophilus influenzae isolated during population-based surveillance for meningitis in Salvador, Brazil.

Antimicrobial susceptibility was determined for 150 Haemophilus influenzae isolates obtained during population-based surveillance for meningitis in Salvador, Brazil. Ten (6.7%) isolates were resistant to ampicillin and chloramphenicol. Of these, two isolates, a beta-lactamase and non-beta-lactamase producer, were resistant to amoxacillin-clavulinic acid. These findings indicate that present antibiotic regimens in Brazil may not be appropriate for the treatment of H. influenzae meningitis.

Amoxicillin-Potassium Clavulanate Combination↗

PubMed2002

Rapid translocation of polarized MDCK cell monolayers by Leptospira interrogans, an invasive but nonintracellular pathogen.

Pathogenic spirochetes of the genus Leptospira are a major cause of human zoonotic infectious disease worldwide. After gaining entry through the skin, the organism causes disease by hematogenously disseminating to multiple organs. The mechanism by which it penetrates the mammalian cell barriers to disseminate is not well understood. In this study, we used a low-passage-number isolate of Leptospira interrogans to elucidate the invasive potential of this spirochete. Quantification of bacteria by dark-field microscopy revealed that pathogenic spirochetes were able to translocate through polarized MDCK cell monolayers at a rate significantly greater than that of nonpathogenic Leptospira or a recognized invasive bacterial pathogen, Salmonella: In contrast to Salmonella, L. interrogans did not alter transepithelial electrical resistance during cell translocation. Both transmission and scanning electron microscopy revealed tight association of the extracellular spirochetes with the host cell plasma membrane, without membrane perturbations suggestive of cytoskeletal rearrangement. Spirochetes were not observed within intercellular junctions or membrane-bound compartments inside cells. They were found within the cytoplasm of only 8% of the counted cells. These results indicate that Leptospira is an invasive but not a facultative intracellular organism. We propose that the rapid translocation of mammalian cells by pathogenic Leptospira is a mechanism designed to evade killing by host cells that permits the organism to quickly reach the bloodstream and disseminate to multiple organs.

Animals↗

PubMed2002

Population-based survey of antimicrobial susceptibility and serotype distribution of Streptococcus pneumoniae from meningitis patients in Salvador, Brazil.

Penicillin-nonsusceptible strains were isolated from 15% of 303 individuals with pneumococcal meningitis identified during a 4-year surveillance study in Salvador, Brazil. The estimated rate of coverage of the seven-valent conjugate vaccine was 74% among patients <5 years of age and 94% among those infected with nonsusceptible isolates, indicating that the use of conjugate vaccines may be an approach to the control of emerging penicillin resistance in Brazil.

Anti-Bacterial Agents↗

PubMed2002

Population-based case-control investigation of risk factors for leptospirosis during an urban epidemic.

Between March and October 2000, 157 suspected cases of leptospirosis hospitalized with complications of Weil's syndrome and a mortality of 8% were identified in Salvador, Brazil. We conducted a population-based case-control study to identify risk factors for acquisition of leptospirosis in neighborhoods with high endemicity during the rainy season-associated urban epidemic. Sixty-six (65%) of 101 laboratory-confirmed cases and 125 age and sex-matched healthy neighborhood controls were interviewed. Residence in proximity to an open sewer (matched odds ratio [OR] = 5.15, 95% confidence interval [CI] = 1.80-14.74), peri-domiciliary sighting of rats (OR = 4.49, 95% CI = 1.57-12.83), sighting groups of five or more rats (OR = 3.90, 95% CI = 1.35-11.27), and workplace exposure to contaminated environmental sources (OR = 3.71, 95% CI = 1.35-10.17) were found to be independent risk factors for acquiring disease. Some of these risk factors are amenable to focused interventions, which include provision of closed drainage systems for sewage and reduction of rodent populations in the peri-domicilary environment. Environmental control of transmission may help to greatly reduce the incidence of severe leptospirosis.

Adolescent↗