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J S Peiris

Publications and source records attributed to J S Peiris.

At least 19 recordsLinked to original sources
PubMed2004

Responsiveness to a pandemic alert: use of reverse genetics for rapid development of influenza vaccines.

BACKGROUND: In response to the emergence of severe infection capable of rapid global spread, WHO will issue a pandemic alert. Such alerts are rare; however, on Feb 19, 2003, a pandemic alert was issued in response to human infections caused by an avian H5N1 influenza virus, A/Hong Kong/213/03. H5N1 had been noted once before in human beings in 1997 and killed a third (6/18) of infected people. The 2003 variant seemed to have been transmitted directly from birds to human beings and caused fatal pneumonia in one of two infected individuals. Candidate vaccines were sought, but no avirulent viruses antigenically similar to the pathogen were available, and the isolate killed embryonated chicken eggs. Since traditional strategies of vaccine production were not viable, we sought to produce a candidate reference virus using reverse genetics. METHODS: We removed the polybasic aminoacids that are associated with high virulence from the haemagglutinin cleavage site of A/Hong Kong/213/03 using influenza reverse genetics techniques. A reference vaccine virus was then produced on an A/Puerto Rico/8/34 (PR8) backbone on WHO-approved Vero cells. We assessed this reference virus for pathogenicity in in-vivo and in-vitro assays. FINDINGS: A reference vaccine virus was produced in Good Manufacturing Practice (GMP)-grade facilities in less than 4 weeks from the time of virus isolation. This virus proved to be non-pathogenic in chickens and ferrets and was shown to be stable after multiple passages in embryonated chicken eggs. INTERPRETATION: The ability to produce a candidate reference virus in such a short period of time sets a new standard for rapid response to emerging infectious disease threats and clearly shows the usefulness of reverse genetics for influenza vaccine development. The same technologies and procedures are currently being used to create reference vaccine viruses against the 2004 H5N1 viruses circulating in Asia.

Animals↗
PubMed2004

Continuing evolution of H9N2 influenza viruses in Southeastern China.

H9N2 influenza viruses are panzootic in domestic poultry in Eurasia and since 1999 have caused transient infections in humans and pigs. To investigate the zoonotic potential of H9N2 viruses, we studied the evolution of the viruses in live-poultry markets in Hong Kong in 2003. H9N2 was the most prevalent influenza virus subtype in the live-poultry markets between 2001 and 2003. Antigenic and phylogenetic analysis of hemagglutinin (HA) showed that all of the 19 isolates found except one belonged to the lineage represented by A/Duck/Hong Kong/Y280/97 (H9N2). The exception was A/Guinea fowl/NT184/03 (H9N2), whose HA is most closely related to that of the human isolate A/Guangzhou/333/99 (H9N2), a virus belonging to the A/Chicken/Beijing/1/94-like (H9N2) lineage. At least six different genotypes were recognized. The majority of the viruses had nonstructural (and HA) genes derived from the A/Duck/Hong Kong/Y280/97-like virus lineage but had other genes of mixed avian virus origin, including genes similar to those of H5N1 viruses isolated in 2001. Viruses of all six genotypes of H9N2 found were able to replicate in chickens and mice without adaptation. The infected chickens showed no signs of disease, but representatives of two viral genotypes were lethal to mice. Three genotypes of virus replicated in the respiratory tracts of swine, which shed virus for at least 5 days. These results show an increasing genetic and biologic diversity of H9N2 viruses in Hong Kong and support their potential role as pandemic influenza agents.

Animals↗
PubMed2001

Nosocomial outbreak of parvovirus B19 infection in a renal transplant unit.

BACKGROUND: Parvovirus B19 (B19) infection is known to cause chronic infection leading to anemia in immunocompromised patients. Although nosocomial B19 infections in immunocompetent patients have been documented, no outbreaks in immunocompromised patients have been previously reported. Whether transmission can occur from a patient with chronic infection is also unknown. METHODS: An outbreak of B19 infection in a renal transplant unit was investigated by molecular analysis of the virus strains and a case-control study. RESULTS: Three patients had genetically identical virus strains suggesting the occurrence of nosocomial transmission. The index case transmitted infection many weeks after the onset of her clinical symptoms. Other patients at risk of acquiring infection were those most intensively immunosuppressed. Viral load in the serum correlated with the hematological response. A rebound in the viral load was associated with clinical relapse and the failure of i.v. immunoglobulin therapy. CONCLUSION: Nosocomial transmission of B19 can occur from immunocompromised patients even when they are in the chronic stage of the infection. The clinical and virological response to i.v. immunoglobulin therapy is variable and depends on the overall level of immunosuppression of the patient.

Adult↗
PubMed2001

Association of tumour necrosis factor alpha and interleukin 6 levels with cytomegalovirus DNA detection and disease after renal transplantation.

Cytokines such as tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) are thought to be important in the pathogenesis of post-transplant cytomegalovirus (CMV) disease. CMV infection increases the production of TNF-alpha and IL-6. Conversely, TNF-alpha switches on the replication of CMV. To study the association of these two cytokines with CMV activity and disease, TNF-alpha and IL-6 levels were assayed in plasma samples taken serially from three groups of renal transplant recipients. Group A (n = 12) had CMV disease and syndrome; Group B (n = 11) had detectable CMV DNA in plasma or peripheral blood leucocytes without disease, i.e., presumed asymptomatic CMV infection, and Group C (n = 11) had no detectable CMV DNA nor disease. The median peak TNF-alpha levels in patients with CMV disease (Group A) were significantly higher than that in Group B or Group C (P < 0.02) whereas the median peak IL-6 levels in group C patients were significantly lower than that in group A (P < 0.04) or group B (P < 0.03). A TNF-alpha level of above 100 pg/ml was significantly associated with CMV disease and high plasma CMV load (> 10,000 copies/ml). IL-6 levels above 15 pg/ml were significantly associated with CMV DNA detection, but not with CMV disease or elevated CMV load. High levels of TNF-alpha or IL-6 were not associated with CMV donor/recipient serostatus, HHV-6 or HHV-7 DNA detection, immunosuppressive regimen or rejection episodes. The role of TNF-alpha in the pathogenesis of CMV disease deserves further investigation.

Adult↗
PubMed2001

Epstein-Barr virus (EBV) infection in infancy.

BACKGROUND: Epstein-Barr virus (EBV) has been shown to be the cause of infectious mononucleosis (IM) and has more complicated associations with several malignant diseases. These EBV associated diseases provide a strong incentive for the development of an EBV vaccine. Most primary EBV infection during infancy and early childhood is mild or subclinical. Little is known about its infection in infancy. The pattern of EBV serological response during infancy may be important for vaccine management. OBJECTIVES: this study has served to clarify the epidemiology and serology of primary EBV infection during early infancy. STUDY DESIGN: longitudinal serum samples from 66 Hong Kong infants were tested for EBV antibodies by immunofluorescence. Cord blood and sequential serum samples from these infants were taken at birth and then at 4-month intervals up to 2 years of age. RESULTS: maternal antibodies were present at different levels in all cord blood specimens and in serum samples of 8 infants at 4-month of age. Evidenced by VCA-IgG seroconversion, 60.6% (40/66) infants were infected during the first 2 years of life. One episode occurred before 8 months of age but, thereafter and for the remaining 16 months of follow-up until the infants were 2 years of age, the infection occurred at essentially a constant rate affecting about 20% of the remaining seronegative infants every 4 months. CONCLUSIONS: the abrupt onset of the infection after a delay of 8 months is a remarkable feature of primary EBV infection during infancy, which implicates a protective role for maternal antibodies. Persisting maternal antibodies may additionally serve to contain the infection once it occurred. This may partly explain why, unlike during adolescence, primary EBV infection early in life is usually asymptomatic.

Antibodies, Viral↗
PubMed2001

The prevalence and characterization of verotoxin-producing Escherichia coli isolated from cattle and pigs in an abattoir in Hong Kong.

The aim of the study was to define the prevalence of verotoxin-producing Escherichia coli (VTEC) in cattle and pigs in a Hong Kong abattoir. Faecal and carcass samples collected from 986 cattle and 487 pigs from an abattoir were tested for verotoxin (VT) by PCR and cytotoxicity assays. VTEC was isolated from 415 and 1-8% of cattle faecal and carcass samples and from 2.1 and 0.2% of porcine faecal and carcass samples, respectively. Amongst 409 VTEC isolates from cattle, 9 were serotype O157:H7 and eaeA+. The most prevalent vt genotype among bovine VTEC was vtl+vt2 (73.8%) and in porcine VTEC was vt2e+ (30%). None of the porcine VTEC isolates and 9.3% of the bovine VTEC isolates was eaeA+. The non-O157 serogroup VTEC isolates carrying eaeA and EHEC-hlyA belonged to serogroups O172, O15, O84, O91, O110 and O121. The local dietary preference for pork or chicken (rather than beef), the low VTEC carriage in pigs, the rarity of additional virulence factors (caeA) in VTEC isolated from cattle may explain the apparently low incidence of human diarrhoeal disease associated with VTEC in Hong Kong hitherto. However, the presence of non-O157 VTEC strains carrying the eacA virulence marker in cattle highlights the fact that sole reliance on sorbitol-MacConkey agar for screening human VTEC isolates may underestimate the human disease burden. The changing dietary habits of the population in Hong Kong reinforce the need for continued vigilance.

Abattoirs↗
PubMed2001

Epstein-Barr virus (EBV) DNA in sera of patients with primary EBV infection.

Detection of Epstein-Barr Virus (EBV) DNA by PCR in serum had a sensitivity of 80%, a specificity of 94%, and positive and negative predictive values of 95 and 79%, respectively, for the diagnosis of primary EBV infection. We suggest that this is a useful addition to the panel of tests used for this purpose.

DNA, Viral↗
PubMed2001

Cocirculation of avian H9N2 and contemporary "human" H3N2 influenza A viruses in pigs in southeastern China: potential for genetic reassortment?

Pigs are permissive to both human and avian influenza viruses and have been proposed to be an intermediate host for the genesis of pandemic influenza viruses through reassortment or adaptation of avian viruses. Prospective virological surveillance carried out between March 1998 and June 2000 in Hong Kong, Special Administrative Region, People's Republic of China, on pigs imported from southeastern China, provides the first evidence of interspecies transmission of avian H9N2 viruses to pigs and documents their cocirculation with contemporary human H3N2 (A/Sydney/5/97-like, Sydney97-like) viruses. All gene segments of the porcine H9N2 viruses were closely related to viruses similar to chicken/Beijing/1/94 (H9N2), duck/Hong Kong/Y280/97 (H9N2), and the descendants of the latter virus lineage. Phylogenetic analysis suggested that repeated interspecies transmission events had occurred from the avian host to pigs. The Sydney97-like (H3N2) viruses isolated from pigs were related closely to contemporary human H3N2 viruses in all gene segments and had not undergone genetic reassortment. Cocirculation of avian H9N2 and human H3N2 viruses in pigs provides an opportunity for genetic reassortment leading to the emergence of viruses with pandemic potential.

Animals↗
PubMed2000

Association of human herpesvirus 7 with cytomegalovirus disease in renal transplant recipients.

BACKGROUND: Recent studies have linked human herpesviruses 6 (HHV-6) and 7 (HHV-7) with posttransplant cytomegalovirus (CMV) disease. METHODS: Thirty-seven renal transplant recipients were monitored weekly for CMV, HHV-6, and HHV-7 DNA and serological responses for 12 weeks after transplantation. Plasma CMV load and the occurrence of CMV disease was related to HHV-6 and -7 detection. RESULTS: CMV disease was identified in 12 patients. In a logistic regression analysis, factors significantly associated with CMV disease were the detection of HHV-7 DNA in peripheral blood leucocytes and donorrecipient CMV serostatus. Patients with detectable HHV-7 DNA had significantly higher peak plasma CMV loads (P=0.01). CONCLUSIONS: An association was found between HHV-7, but not HHV-6, DNA detection and CMV disease, suggesting a possible role of HHV-7 in its pathogenesis.

Cytomegalovirus↗
PubMed2000

Use of oral valaciclovir in a 12-year-old boy with herpes simplex encephalitis.

We report on a 12-year-old boy with herpes simplex encephalitis, in whom a severe localised skin reaction developed following the infusion of intravenous acyclovir. Oral valaciclovir was given as continuation therapy to complete the 3-week course of antiviral treatment and resulted in complete recovery without side effects. This report illustrates the advantage of using the polymerase chain reaction to diagnose herpes simplex encephalitis and the potential use of newer antiviral agents, such as valaciclovir, as continuation therapy in the management of the infection. The higher oral bioavailability of newer antiviral agents allows part of the extended treatment period of patients with herpes simplex encephalitis to be carried out as an ambulatory oral regimen.

Acyclovir↗
PubMed1998

Clinical significance of alimentary tract microbes in bone marrow transplant recipients.

A prospective study on the microbes isolated from the alimentary tract in 120 bone marrow transplant (BMT) recipients (1991-1993) was undertaken to define the spectrum of organisms isolated under antimicrobial prophylaxis, their temporal sequence of emergence, and the associated morbidity and mortality. Clostridium difficile (n = 20), isolated in the pre-engraftment and early post-engraftment periods (day 2-45 post-BMT), was the most common microbe recovered from stool of patients with diarrhea. In contrast to previous reports, no significant difference in mortality was observed between patients with and without C. difficile isolated in stool. Two patients had neutropenic ileocecitis with concomitant bacteremia due to Escherichia coli and Klebsiella pneumoniae. One patient was found to have astrovirus gastroenteritis (day 7), and Giardia lamblia was recovered from the stool of another (day -7). Heavy growth of Staphylococcus aureus from direct smear-positive specimens was found from the upper airway of two patients with severe mucositis and complete dysphagia (day 12 and 23). Salmonella spp. of groups B and E were found in the stool of five asymptomatic patients at the time of conditioning. No specific organisms was recovered from the endoscopic brushing of two patients with lower end esophagitis, three patients with upper gastrointestinal bleeding, and three patients with perirectal cellulitis. During the post-engraftment period, five patients had documented cytomegalovirus gastroenterocolitis (days 34-97), one had Mycobacterium chelonae colitis (day 70), and another had nodular gastritis due to Acremonium falciforme (day 270). Overall, only 28% of patients with alimentary tract symptoms/syndrome had specific pathogens isolated from clinical specimens. Differentiation of the causation of alimentary tract symptoms was often difficult because noninfectious complications such as conditioning toxicity, graft-versus-host disease, and its treatment often caused alimentary tract symptoms in addition to predisposed BMT patient to infection. The reluctance of obtaining tissue biopsy for ascertaining the importance of those potential alimentary tract pathogens often dictate the use of empirical treatment.

Adolescent↗
PubMed1998

Inpatient emergencies encountered by an infectious disease consultative service.

The spectrum of infectious disease (ID) emergencies in hospitalized patients was assessed in a prospective study of 3,626 inpatient ID consultations in a 1,350-bed teaching hospital. ID emergencies, defined by a need or anticipated need for advanced life support or by irreversible organ damage leading to permanent functional loss, were encountered in 175 patients. Infections of the central nervous system (26.3%), cardiovascular system (14.9%), alimentary system (13.1%), and lower respiratory tract (7.4%) and adverse reactions to antimicrobial agents (7.4%) were most common. In 18.9% of the cases, the referring clinicians were unaware of the emergency at the time of referral. Drug reactions (46.1%), severe alimentary and peritoneal infections (32.0%), upper respiratory tract infections (28.6%), and skin and soft-tissue infections (27.3%) were most frequently missed. The emergency ID conditions were not recognized because they had an atypical presentation (51.5%), were not commonly seen in the referring specialty (24.2%), were due to rare organisms (15.2%), or had unusual anatomical sites of involvement (9.1%). A close liaison between clinicians and the ID team is crucial for recognition of ID emergencies at their early stages so that appropriate investigations and management can be instituted expediently, before the occurrence of irreversible damage.

Adult↗
PubMed1998

Development and evaluation of an Epstein-Barr virus (EBV) immunoglobulin M enzyme-linked immunosorbent assay based on the 18-kilodalton matrix protein for diagnosis of primary EBV infection.

A new immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) based on the recombinant Epstein-Barr virus (EBV) matrix protein was developed. Compared to indirect immunofluorescence for the detection of IgM antibody to the EBV capsid antigen on clinical specimens, the sensitivity and specificity of the new IgM ELISA were 96 and 96%, respectively.

Antibodies, Viral↗
PubMed1997

Correlation between the detection of viral DNA by the polymerase chain reaction in peripheral blood leukocytes and serological responses to human herpesvirus 6, human herpesvirus 7, and cytomegalovirus in renal allograft recipients.

Diagnosis of significant infections by human herpesvirus 6 (HHV6) and 7 (HHV7) in transplant patients has proved difficult because both viruses are ubiquitous and can cause persistent infections in their hosts. The significance of viral DNA detected in peripheral blood leukocytes (PBLs; DNAemia) by PCR is therefore unclear. The interpretation of serological results is complicated by the fact that both primary and secondary infections with other herpesviruses may be associated with a concurrent antibody response to HHV6. Fifty-four renal allograft recipients were studied prospectively and their serological response to HHV6, HHV7 and CMV were compared with the detection of viral DNAemia from the homologous and heterologous viruses. Serum and heparinished blood samples were collected prospectively from 54 renal allograft recipients. DNA was extracted from PBLs and tested for the presence of HHV6, HHV7 and CMV DNA by PCR. Antibodies to HHV6 and HHV7 were measured by an indirect immunofluorescence test and to CMV by an anticomplement immunofluorescence (ACIF) test. CMV IgM antibodies were detected by a commercial enzyme immunoassay. CMV and HHV7 DNAemia were each significantly associated with serological responses to the homologous virus but no such association was found for HHV6 DNAemia. However, patients with consecutively positive DNAemia to any of the viruses (including HHV6) were more likely to have a homologous serological response. Patients who had detectable CMV IgM without a concurrent rise in CMV antibodies were significantly less likely to have CMV DNAemia (odds ratio = 0.16; 95% CI 0.02-0.9). CMV IgM antibodies may be associated with HHV6 or HHV7 DNAemia (odds ratio 2.3; 95% CI 0.5-15). This serological profile may reflect a crossreactive response to HHV6, HHV7 or other herpesviruses. CMV IgM should not be used in isolation for the diagnosis of CMV infection or disease in this group of patients.

Adolescent↗
PubMed1997

Human herpesvirus-6 and human herpesvirus-7 infections in bone marrow transplant recipients.

Human cytomegalovirus (HCMV), human herpesvirus-6 (HHV-6), and human herpesvirus-7 (HHV-7) DNA in peripheral blood leukocytes (PBL) of 61 bone marrow transplant recipients was monitored weekly during the first 12 weeks post-transplantation by a nested polymerase chain reaction (PCR). Thirty-seven (61%), 17 (28%), and 32 (53%) of patients had one or more PBL specimens positive for HCMV, HHV-6 or HHV-7 DNA, respectively. HHV-7 DNA in PBL during the early post-transplant period was associated with a longer time to neutrophil engraftment (mean 28.8 days vs 19.8 days; P = 0.01). In two patients who failed to engraft, HHV-6 DNA and HHV-7 DNA was detected in plasma and PBL, respectively, early in their post-transplant period. Patients with HCMV disease were more likely to have concurrent HHV-7 DNA in PBL prior to onset of disease than were patients with asymptomatic HCMV infection, suggesting that HHV-7 may be a cofactor in the progression from HCMV infection to HCMV disease. In the 17 patients (179 specimens) in whom viral DNA in plasma was studied (in addition to PBL), a positive result was found only in 3. In each, viral DNA in plasma appeared to correlate with clinically significant disease. HHV-7 DNA in plasma was associated with encephalitis in an allograft recipient.

Acyclovir↗
PubMed1997

Distinct genotypic distributions of cytomegalovirus (CMV) envelope glycoprotein in bone marrow and renal transplant recipients with CMV disease.

A prospective study of the spectrum of glycoprotein B (gB) and glycoprotein H (gH) genotypes of cytomegalovirus (CMV) was conducted with five categories of patients: viremic bone marrow-transplant (BMT) recipients who developed CMV disease after BMT (n = 22), viremic BMT recipients without CMV disease (n = 11), viremic renal-transplant recipients who developed CMV disease after transplantation (n = 14), viremic renal-transplant recipients without CMV disease (n = 13), and premature babies with asymptomatic congenital CMV infections (n = 13). Genotypic stability was observed because the gB and gH genotypes of multiple isolates obtained from a single patient were identical. The distribution of gH genotypes in patients of all groups studied were similar. However, there was a unique distribution of the gB genotype in the first category of patients, i.e., BMT recipients with CMV disease, which was distinct from those of all other categories (P < 0.05). CMV isolates from 54% of BMT recipients with CMV disease exhibited gB type 2, while isolates from 46, 50, 69, and 77% of the BMT recipients without CMV disease, renal-transplant recipients with and those without CMV disease, and premature babies with congenital CMV infection, respectively, were of gB type 1. An analysis of the clinical characteristics of BMT recipients with CMV disease indicated that all underwent either an allogeneic or matched, unrelated donor transplant, and half had severe acute graft-versus-host disease (grades 2 to 4). The statistically significant genotypic difference between CMV isolates from BMT recipients with and without CMV disease was not observed between isolates from renal-transplant recipients with and without CMV disease. We speculate that differences in pathogenesis in different patient groups might account for these observations. These findings would also facilitate decision making about the choice of recombinant CMV glycoprotein vaccine required to immunize transplant donors and the subsequent adoptive transfer of immunity to BMT recipients. When the source of CMV DNA required for genotyping was investigated among renal-transplant recipients, direct use of peripheral blood leukocytes was 95% effective compared to the effectiveness of cells obtained from conventional culture of peripheral blood specimens.

Adult↗
PubMed1997

Detection of CMV DNA in bone marrow transplant recipients: plasma versus leucocyte polymerase chain reaction.

AIMS: To compare the nested polymerase chain reaction (PCR) assay for the detection of cytomegalovirus (CMV) DNA in peripheral blood leucocytes and plasma obtained from heparinised blood; to determine the efficiency of various DNA extraction methods to minimise inhibition of plasma PCR and their effect on the sensitivity of plasma PCR; to determine the inhibitory effect of heparin, dextran, and EDTA on the CMV PCR assay. METHODS: 217 heparinised blood specimens from 58 bone marrow transplant patients were processed and the sensitivities and specificities of the PCR assays using peripheral blood leucocytes and plasma (with simple, Instagene, and Geneclean extraction methods) were compared to those of conventional CMV culture. In a separate experiment, dilutions of heparin, dextran, and EDTA were included in PCR assays. RESULTS: The detection of CMV DNA using peripheral blood leucocytes for PCR assay was significantly more sensitive (100%) than when using plasma (60%). Instagene and Geneclean extraction removed inherent inhibition but did not improve the sensitivity of the plasma PCR reaction. Heparin had an inhibitory effect on PCR. CONCLUSIONS: PCR assay using peripheral blood leucocytes is better than plasma for guiding the prescription of ganciclovir to bone marrow transplant patients. Heparin is inhibitory to the plasma PCR reaction.

Bone Marrow Transplantation↗