Biomedical subjects
Publications and source records attributed to Ivan F N Hung.
Trichuris trichiura is a worldwide problem affecting millions of people. We report an unusual case of intussusception caused by T. trichiura that mimics acute appendicitis. The literature on T. trichiura associated intussusception is reviewed.
The pathogenesis of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) at the cellular level is unclear. No human cell line was previously known to be susceptible to both SARS-CoV and other human coronaviruses. Huh7 cells were found to be susceptible to both SARS-CoV, associated with SARS, and human coronavirus 229E (HCoV-229E), usually associated with the common cold. Highly lytic and productive rates of infections within 48 h of inoculation were reproducible with both viruses. The early transcriptional profiles of host cell response to both types of infection at 2 and 4 h postinoculation were determined by using the Affymetrix HG-U133A microarray (about 22,000 genes). Much more perturbation of cellular gene transcription was observed after infection by SARS-CoV than after infection by HCoV-229E. Besides the upregulation of genes associated with apoptosis, which was exactly opposite to the previously reported effect of SARS-CoV in a colonic carcinoma cell line, genes related to inflammation, stress response, and procoagulation were also upregulated. These findings were confirmed by semiquantitative reverse transcription-PCR, reverse transcription-quantitative PCR for mRNA of genes, and immunoassays for some encoded proteins. These transcriptomal changes are compatible with the histological changes of pulmonary vasculitis and microvascular thrombosis in addition to the diffuse alveolar damage involving the pneumocytes.
Using clinical samples from patients with severe acute respiratory syndrome, we showed that the sensitivities of a quantitative reverse transcription-polymerase chain reaction (80% for fecal samples and 25% for urine samples) were higher than those of the polyclonal (50% and 5%) and monoclonal (35% and 8%) antibody-based nucleocapsid antigen capture enzyme-linked immunosorbent assays.
An unprecedented community outbreak of severe acute respiratory syndrome (SARS) occurred in the Amoy Gardens, a high-rise residential complex in Hong Kong. Droplet, air, contaminated fomites, and rodent pests have been proposed to be mechanisms for transmitting SARS in a short period. We studied nasopharyngeal viral load of SARS patients on admission and their geographic distribution. Higher nasopharyngeal viral load was found in patients living in adjacent units of the same block inhabited by the index patient, while a lower but detectable nasopharyngeal viral load was found in patients living further away from the index patient. This pattern of nasopharyngeal viral load suggested that airborne transmission played an important part in this outbreak in Hong Kong. Contaminated fomites and rodent pests may have also played a role.
BACKGROUND: Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently. CASE PRESENTATION: We aim to better define this unique clinical syndrome by reporting two cases of PCP manifesting acutely with respiratory failure during reversal of immunosuppression in non-HIV infected patients, and reviewed the relevant literature. We searched our databases for PCP cases manifesting in the context of IRD according to our predefined case definition, and reviewed the case notes retrospectively. A comprehensive search was performed using the Medline database of the National Library of Medicine for similar cases reported previously in the English literature in October 2003. A total of 28 non-HIV (excluding our present case) and 13 HIV-positive patients with PCP manifesting as immunorestitution disease (IRD) have been reported previously in the literature. During immunorestitution, a consistent rise in the median CD4 lymphocyte count (28/microL to 125/microL), with a concomitant fall in the median HIV viral load (5.5 log10 copies/ml to 3.1 log10 copies/ml) was observed in HIV-positive patients who developed PCP. A similar upsurge in peripheral lymphocyte count was observed in our patients preceding the development of PCP, as well as in other non-HIV immunosuppressed patients reported in the literature. CONCLUSIONS: PCP manifesting as IRD may be more common than is generally appreciated. Serial monitoring of total lymphocyte or CD4 count could serve as a useful adjunct to facilitate the early diagnosis and pre-emptive treatment of this condition in a wide range of immunosuppressed hosts, especially in the presence of new pulmonary symptoms and/or radiographic abnormalities compatible with the diagnosis.
BACKGROUND: Severe acute respiratory syndrome (SARS) is caused by a novel coronavirus. It may progress to respiratory failure, and a significant proportion of patients die. Preliminary data suggest that a high viral load of the SARS coronavirus is associated with adverse outcomes in the intensive care unit, but the relation of viral load to survival is unclear. METHODS: We prospectively studied an inception cohort of 133 patients with virologically confirmed SARS who were admitted to 2 general acute care hospitals in Hong Kong from Mar. 24 to May 4, 2003. The patients were followed until death or for a minimum of 90 days. We used Cox proportional hazard modelling to analyze potential predictors of survival recorded at the time of presentation, including viral load from nasopharyngeal specimens (measured by quantitative reverse transcriptase polymerase chain reaction [PCR] of the SARS-associated coronavirus). RESULTS: Thirty-two patients (24.1%) met the criteria for acute respiratory distress syndrome, and 24 patients (18.0%) died. The following baseline factors were independently associated with worse survival: older age (61-80 years) (adjusted hazard ratio [HR] 5.24, 95% confidence interval [CI] 2.03-13.53), presence of an active comorbid condition (adjusted HR 3.36, 95% CI 1.44-7.82) and higher initial viral load of SARS coronavirus, according to quantitative PCR of nasopharyngeal specimens (adjusted HR 1.21 per log10 increase in number of RNA copies per millilitre, 95% CI 1.06-1.39). INTERPRETATION: We found preliminary evidence that higher initial viral load is independently associated with worse prognosis in SARS. Mortality data for patients with SARS should be interpreted in light of age, comorbidity and viral load. These considerations will be important in future studies of SARS.
BACKGROUND: Although the genome of severe acute respiratory syndrome coronavirus (SARS-CoV) has been sequenced and a possible animal reservoir identified, seroprevalence studies and mass screening for detection of subclinical and non-pneumonic infections are still lacking. METHODS: We cloned and purified the nucleocapsid protein and spike polypeptide of SARS-CoV and examined their immunogenicity with serum from patients with SARS-CoV pneumonia. An ELISA based on recombinant nucleocapsid protein for IgG detection was tested with serum from 149 healthy blood donors who donated 3 years previously and with serum positive for antibodies against SARS-CoV (by indirect immunofluorescence assay) from 106 patients with SARS-CoV pneumonia. The seroprevalence of SARS-CoV was studied with the ELISA in healthy blood donors who donated during the SARS outbreak in Hong Kong, non-pneumonic hospital inpatients, and symptom-free health-care workers. All positive samples were confirmed by two separate western-blot assays (with recombinant nucleocapsid protein and recombinant spike polypeptide). FINDINGS: Western-blot analysis showed that the nucleocapsid protein and spike polypeptide of SARS-CoV are highly immunogenic. The specificity of the IgG antibody test (ELISA with positive samples confirmed by the two western-blot assays) was 100%, and the sensitivity was 94.3%. Three of 400 healthy blood donors who donated during the SARS outbreak and one of 131 non-pneumonic paediatric inpatients were positive for IgG antibodies, confirmed by the two western-blot assays (total, 0.48% of our study population). INTERPRETATION: Our findings support the existence of subclinical or non-pneumonic SARS-CoV infections. Such infections are more common than SARS-CoV pneumonia in our locality.
Clinical deterioration during the course of community-acquired infections can occur as a result of an exaggerated immune response of the host towards the inciting pathogens, leading to immune-mediated tissue damage. Whether a surge in the peripheral lymphocyte count can be used as a surrogate marker indicating the onset of immunopathological tissue damage is not known. In this study, we report the clinical presentations and outcomes of a cohort of immunocompetent patients with non-tuberculous community acquired infections who experienced clinical deterioration during hospital stay (n=85). 12 (14.1%) patients had a surge in lymphocyte count preceding their clinical deteriorations, and their diagnoses included viral pneumonitis , viral encephalitis , scrub typhus , leptospirosis , brucellosis , and dengue haemorrhagic fever . The clinical manifestations during deterioration ranged from interstitial pneumonitis , airway obstruction , CNS disturbances , and systemic capillary leak syndrome , all of which were thought to represent immunopathological tissue damages. When compared with patients without lymphocyte surge, these patients were more likely to be infected with fastidious/viral pathogens (0 vs 12; p<0.05), in addition to having lower mean baseline lymphocyte counts (403+/-181 vs 1143+/-686 cells/microl; p<0.05). We postulate that the peripheral lymphocyte count may be a useful surrogate marker indicating the presence of immunopathological damage during clinical deterioration in certain infectious diseases.