Biomedical subjects

K N Ward

Publications and source records attributed to K N Ward.

At least 19 recordsLinked to original sources

PubMed2005

Door-opening motion can potentially lead to a transient breakdown in negative-pressure isolation conditions: the importance of vorticity and buoyancy airflows.

A patient with severe chickenpox was admitted to a negative-pressure isolation room. He remained sedated, intubated and mechanically ventilated throughout his admission. He was managed only by nurses immune to chickenpox. A non-immune male nurse occasionally handed equipment through the doorway, without entering the room. Ten days later, he also developed chickenpox. Sequencing of viruses from the patient and nurse showed the same rare genotype, indicating nosocomial transmission. An experimental model demonstrated that, despite negative pressure, opening the door could have resulted in transport of infectious air out of the isolation room, leading to a breakdown in isolation conditions.

Air Pressure↗

PubMed2005

The natural history and laboratory diagnosis of human herpesviruses-6 and -7 infections in the immunocompetent.

BACKGROUND: Human herpesviruses-6 and -7 (HHV-6/7) are widespread in all populations. In some individuals HHV-6 is found integrated into human chromosomes, which results in a high viral load in blood. HHV-6 variant B (HHV-6B) and HHV-7 primary infections, although usually silent, not infrequently cause the childhood exanthem roseola infantum and are sometimes accompanied by neurological illness. HHV-6 variant A (HHV-6A) is not associated with any disease. OBJECTIVES: The present review focuses on the immunocompetent individual and considers the epidemiology of the two viruses and their role as human pathogens. It discusses the importance of satisfactory diagnostic tests to distinguish them, compares those currently available, and recommends how best to differentiate primary from persistent infection in each case. RESULTS: It is explained that at the present time antibody avidity immunofluorescence tests are the most reliable discriminators of the two types of infection. In primary infection these tests can be supplemented by PCR for viral DNA in blood but careful interpretation is required for HHV-6 in view of the high persistent viral DNA load seen with chromosomal integration. Since the contribution of primary HHV-6 and -7 infections to the burden of severe neurological illness in young children is only now emerging as significant, the need to test for these viruses in such cases is stressed. CONCLUSIONS: 1. Primary HHV-6/7 infections must be distinguished from persistent infections. 2. Chromosomal integration of HHV-6 requires urgent study. 3. HHV-6A/B must be distinguished in clinical situations. 4. Where serious neurological disease/encephalitis is temporally related to immunisation it is particularly important to test for HHV-6/7 primary infection since otherwise the condition might wrongly be diagnosed as a vaccine reaction. 5. Because less is currently known about HHV-7 and HHV-6A than HHV-6B, future studies should concentrate on the former two. 6. Improvements in diagnostic tests are required for each virus.

Exanthema Subitum↗

PubMed2005

The effect of low-dose aciclovir on reactivation of varicella zoster virus after allogeneic haemopoietic stem cell transplantation.

Patients undergoing haemopoietic stem cell transplants (HSCT) are at high risk of varicella zoster virus (VZV) reactivation, with a significant incidence of dissemination. This study reports a retrospective analysis of 247 allogeneic HSCT recipients receiving anti-viral prophylaxis with low-dose oral aciclovir 400 mg/day, administered until immunosuppression was discontinued and the CD4(+) cell count exceeded 200/mm(3). Viral reactivation was successfully suppressed by aciclovir prophylaxis, with only one case of breakthrough infection. The cumulative incidence of zoster infection at 1 year post transplant was 2% and at 5 years 34%. In all, 64 patients discontinued prophylaxis. Zoster developed in 26 of these, giving a cumulative incidence of infection at 1 year after stopping aciclovir of 39% and at 3 years 44%. Infection occurred in a localised dermatomal distribution in 93% of cases. This supports previous findings that aciclovir prophylaxis prevents early VZV reactivation, although the long-term incidence is not affected as infection occurs once prophylaxis is discontinued. Such infection, however, is mild and localised. This study does not support the idea that use of such low-dose aciclovir regimens reduces the zoster incidence by permitting subclinical reactivation during prophylaxis, and therefore the re-establishment of protective anti-viral immunity.

Acyclovir↗

PubMed2005

Human herpesviruses-6 and -7 each cause significant neurological morbidity in Britain and Ireland.

BACKGROUND: Primary human herpesvirus-6 and -7 (HHV-6/-7) infections cause febrile illness sometimes complicated by convulsions and rarely encephalopathy. AIMS: To explore the extent of such HHV-6 and -7 induced disease in young children. METHODS: In a three year prospective study in Britain and Ireland, 205 children (2-35 months old) hospitalised with suspected encephalitis and/or severe illness with fever and convulsions were reported via the British Paediatric Surveillance Unit network. Blood samples were tested for primary HHV-6 and -7 infections. RESULTS: 26/156 (17%) of children aged 2-23 months had primary infection (11 HHV-6; 13 HHV-7; two with both viruses) coinciding with the acute illness; this was much higher than the about three cases expected by chance. All 26 were pyrexial; 25 had convulsions (18 status epilepticus), 11 requiring ventilation. Median hospital stay was 7.5 days. For HHV-6 primary infection the median age was 53 weeks (range 42-94) and the distribution differed from that of uninfected children; for HHV-7, the median was 60 weeks (range 17-102) and the distribution did not differ for the uninfected. Fewer (5/15) children with primary HHV-7 infection had previously been infected with HHV-6 than expected. CONCLUSIONS: Primary HHV-6 and HHV-7 infections accounted for a significant proportion of cases in those <2 years old of severe illness with fever and convulsions requiring hospital admission; each virus contributed equally. Predisposing factors are age for HHV-6 and no previous infection with HHV-6 for HHV-7. Children with such neurological disease should be investigated for primary HHV-6/-7 infections, especially in rare cases coinciding by chance with immunisation to exclude misdiagnosis as vaccine reactions.

Child, Preschool↗

PubMed2004

Herpes simplex encephalitis: an audit of the use of laboratory diagnostic tests.

BACKGROUND: The combination of both PCR and intrathecal antibody studies is recommended to confirm or refute the diagnosis of herpes simplex encephalitis (HSE). AIM: To investigate the pattern of use of laboratory tests in the diagnosis of suspected cases of HSE, and to determine the final diagnosis in cases proven not to be HSE. DESIGN: Structured audit. METHODS: We reviewed the case-notes of all patients who, over a five-year time period, presented with suspected encephalitis; and/or were prescribed aciclovir. Clinical and laboratory criteria were used to categorize the likelihood of HSE. RESULTS: We identified 222 patients: 10 (5%) had definite HSE, 24 (10%) possible HSE, and 144 (65%) a definite alternative diagnosis. In 44 (20%), no final diagnosis was made, but the diagnosis of HSE was excluded. PCR was performed in 68 (31%), intrathecal antibody studies in 24 (11%), and brain biopsy in 17 (8%). A wide range of diseases mimicked HSE, but most common were inflammatory diseases and other infections of the central nervous system. DISCUSSION: Laboratory tests, particularly intrathecal antibody assays, are under-used in the diagnosis of HSE. Although early empirical treatment of suspected HSE is essential, confirmation or exclusion of the diagnosis is equally important to avoid overlooking alternative diagnoses. Identification of the aetiology of encephalitis is of particular importance, given the current concerns of emerging infections and bioterrorism.

Acyclovir↗

PubMed2003

Primary human herpesvirus-6 and -7 infections, often coinciding, misdiagnosed as measles in children from a tropical region of Brazil.

We investigated primary human herpesvirus-6 and -7 (HHV-6, HHV-7) infections as a cause of rashes incorrectly diagnosed as measles in Brazilian children. Sera from 124 patients, aged 4 months to 17 years, from the states of Rio de Janeiro and Espirito Santo, in whom measles, rubella and parvovirus B19 infections had been excluded, were studied using indirect immunofluorescence antibody avidity tests; 38 (31%) had evidence of primary HHV-6 and/or HHV-7 infections. Twenty four children had primary HHV-6 infection, either recent or coincident with the rash, and similarly 31 had primary HHV-7 infection. Remarkably, almost half (17) of primary infections were dual HHV-6 and HHV-7 infections with the majority, 12 (71%), in children less than 1 year old. HHV-7 infection occurred earlier than previously reported, perhaps due to socioeconomic and tropical conditions in this region of Brazil, and thus coincided with the HHV-6 infections. This study also highlights the difficulties of diagnosing a rash illness on clinical grounds alone.

Adolescent↗

PubMed2003

Brain stem encephalitis caused by primary herpes simplex 2 infection in a young woman.

A 27 year old woman developed a vesicular genital rash and cerebellar dysfunction with progressive neurological deterioration suggesting brain stem encephalitis. Respiratory support was required. Magnetic resonance imaging (MRI) of the brain on day 7 showed signal hyperintensity in the central medulla and ventral pons, typical of acute inflammation. The course was severe and relapse occurred. MRI on day 33 showed a haemorrhagic area in the medulla. Treatment with aciclovir/valaciclovir eventually led to gradual recovery. Herpes simplex virus 2 (HSV-2) DNA was detected in CSF on days 11 and 14. HSV-2 was also detected in vesicle fluid from the genital rash. Serum was initially negative for HSV-1 and HSV-2 antibodies, but convalescent samples showed seroconversion to HSV-2, indicating primary infection. Intrathecal synthesis of oligoclonal IgG bands specific for HSV was identified in the CSF. It is important to differentiate HSV-2 from HSV-1, and primary from initial or reactivated infection, so that prolonged aciclovir treatment followed by prophylaxis is instituted to prevent the high likelihood of symptomatic relapse in primary HSV-2 infection.

Acyclovir↗

PubMed2002

Neuroinvasion during delayed primary HHV-7 infection in an immunocompetent adult with encephalitis and flaccid paralysis.

Antibody avidity tests have been used to detect primary human herpesvirus-7 (HHV-7) infection in an immunocompetent 19-year-old man with encephalitis and flaccid paralysis for which all other suspected causes had been excluded. The finding of the viral DNA in the cerebrospinal fluid (CSF) but not in serum samples suggests that primary HHV-7 infection with invasion of the central nervous system and consequential disease had occurred. As almost all adults are infected with HHV-7 in early childhood, the present case of delayed primary infection with serious symptoms must be exceptionally rare and no cases of such late acquisition of the virus have been documented in the literature. This report of HHV-7 DNA in the CSF of an immunocompetent adult is also unique.

Adult↗

PubMed2002

Evaluation of the specificity and sensitivity of indirect immunofluorescence tests for IgG to human herpesviruses-6 and -7.

Sera from 118 children aged up to 4 years were tested by indirect immunofluorescence for human herpesvirus-6 and -7 (HHV-6 and HHV-7) antibodies. Antibody results were confirmed as true positives if the relevant viral DNA was detected in saliva or, in some cases of primary infection, by the finding of the relevant DNA in cerebrospinal fluid or serum. Results from samples taken from the 15 children less than 6 months old showed that HHV-6 and/or HHV-7 antibody was either absent or present at low titre suggesting persistent maternal antibody rather than true infection. The sensitivity, specificity, positive and negative predictive values of the HHV-6 IgG test were therefore based on the data from the 103 children older than 6 months and the results were 95, 84, 91 and 90%, respectively. Likewise, the sensitivity, specificity, positive and negative predictive values of the HHV-7 IgG test were 95, 76, 84 and 93%, respectively. There was limited cross-reactivity between HHV-6 and HHV-7 antibodies; where both HHV-6 and HHV-7 antibodies are detected, titres above 32 may be accepted as true positives but lower titres require confirmation by detection of the relevant viral DNA or, in the case of primary infection, by a rising antibody titre.

Antibodies, Viral↗

PubMed2002

Human herpesvirus-7 infection of the CNS with acute myelitis in an adult bone marrow recipient.

The beta-herpesviruses, human herpesviruses-6 and -7 (HHV-6 and HHV-7), are closely related and have very similar biological behaviour. While HHV-6 is associated with encephalitis in immunosuppressed adults, HHV-7 is not recognised as a cause of neurological disease in such patients. This report describes the identification of a reactivated HHV-7 infection in the cerebrospinal fluid of an adult who presented with an acute myelitis 11 months after unrelated donor bone marrow transplant.

Anti-Inflammatory Agents↗

PubMed2001

Respiratory virus infections after stem cell transplantation: a prospective study from the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation.

Community-acquired respiratory virus infections are a cause of mortality after stem cell transplantation (SCT). A prospective study was performed at 37 centers to determine their frequency and importance. Additional cases were also collected to allow the analysis of risk factors for severe infection. Forty episodes were collected in the prospective study and 53 additional episodes through subsequent case collection. The frequency of documented respiratory virus infections was 3.5% among 819 allogeneic and 0.4% among 1154 autologous SCT patients transplanted during the study period. The frequency of lower respiratory tract infections (LRTI) was 2.1% among allogeneic and 0.2% among autologous SCT patients. The mortality within 28 days from diagnosis of a respiratory viral infection was 1.1% among allogeneic SCT while no autologous SCT patient died. The deaths of five patients (0.6%) were directly attributed to a respiratory virus infection (three RSV; two influenza A). On multivariate analysis, lymphocytopenia increased the risk for LRTI (P = 0.008). Lymphocytopenia was also a significant risk factor for LRTI in patients with RSV infections. The overall mortality in RSV infection was 30.4% and the direct RSV-associated mortality was 17.4%. For influenza A virus infection, the corresponding percentages were 23.0% and 15.3%. This prospective study supports the fact that community-acquired respiratory virus infections cause transplant-related mortality after SCT.

Adolescent↗

PubMed2001

Use of immunoglobulin G antibody avidity for differentiation of primary human herpesvirus 6 and 7 infections.

A human herpesvirus 7 (HHV-7) indirect immunofluorescence antibody avidity test was developed and used with an existing human herpesvirus 6 (HHV-6) antibody avidity test to detect and distinguish low-avidity antibodies to HHV-6 and HHV-7 and hence the respective primary infections. With sera from 269 British children aged 0 to 179 weeks, the tests showed that most (10 of 98 serum samples [13%]) HHV-6 low-avidity antibody was found in the first year of life, whereas for HHV-7, most (18 of 101 serum samples [20%]) HHV-7 low-avidity antibody was found in the second year of life. Five children had low-avidity antibodies to both viruses. Of nine Japanese children with previously serologically proven primary HHV-6 or HHV-7 infections, eight had low-avidity antibody only to the relevant virus, but one child had low-avidity antibodies to HHV-6 and HHV-7. The avidity tests were applied to five British children and further proof of viral infection was sought by the detection of specific DNA in serum or plasma, and saliva or cerebrospinal fluid. In two children who had low-avidity antibody to HHV-7 but who were seronegative for HHV-6, only HHV-7 was found. Both viruses were detected in one child with low-avidity HHV-7 antibody and high-avidity HHV-6 antibody. In two children with low-avidity antibodies to both viruses, HHV-6 and HHV-7 DNAs were found, confirming dual primary infections and excluding antibody cross-reactivity.

Adult↗

PubMed1999

A comparison of prophylactic vs pre-emptive ganciclovir to prevent cytomegalovirus disease after T-depleted volunteer unrelated donor bone marrow transplantation.

The prophylactic and pre-emptive use of ganciclovir (GCV) both reduce significantly the incidence of CMV disease after sibling BMT but it is unclear which of these strategies is best for volunteer unrelated donor (VUD) BMT patients. We reviewed 49 consecutive patients, who received a T-depleted VUD BMT (from March 1990 to March 1996) for the treatment of CML in chronic phase, and were CMV seropositive before transplant or had a CMV seropositive donor. Patients were conditioned with cyclophosphamide (120 mg/kg for 2 days) and total body irradiation (13.2-14.4 Gy). Prophylaxis for GVHD was cyclosporin A and methotrexate with ex vivo or in vivo T cell depletion. Twenty-seven patients received pre-emptive GCV if CMV infection was detected by short-term culture before day +120 post BMT. Twenty-two patients received prophylactic GCV from engraftment until day +120 post BMT. The probabilities of CMV infection and disease occurring by 1 year post-BMT were greater in the pre-emptive GCV group than in the prophylactic GCV group (73.8% and 64.0% vs 53.1% and 30.0%, respectively; P=0.04 and 0.07). The incidence of death from CMV disease was similar in both groups (3/12 (25%) vs 3/10 (30%), respectively) and there was no difference in 1 year survival (55.6% vs 54.2%, respectively). New strategies are urgently required for the prevention of CMV disease after T-depleted VUD BMT.

Adult↗

PubMed1999

Management of human cytomegalovirus infection and disease after allogeneic bone marrow transplantation.

BACKGROUND AND OBJECTIVE: Human cytomegalovirus (HCMV) infection and disease remain a major cause of morbidity and mortality after bone marrow transplantation. HCMV disease, especially pneumonitis, may be treated with ganciclovir and immunoglobulin but even so the outcome is poor with mortality rates of 30-70%. It is therefore imperative to treat HCMV infection before it develops into disease. The aim of this article is to describe the main strategies used to prevent HCMV infection and to improve the survival after CMV disease in bone marrow transplant recipients. INFORMATION SOURCES: In the present review, we examined personal papers in this field and articles published in journals covered by the Science Citation Index and Medline. STATE OF THE ART: Major advances have been made in preventing HCMV infection and disease through two different approaches, both of which reduce HCMV induced morbidity and mortality: In pre-emptive therapy, patients are given ganciclovir when HCMV infection is first identified and this is continued 3-4 months after transplantation; in prophylactic therapy ganciclovir is given to all patients at risk of HCMV disease from engraftment up to 3-4 months post transplantation. Each strategy has advantages and disadvantages and there is no evidence for the superiority of one over the other since the overall survival is the same and the incidence of death from HCMV disease is similar. PERSPECTIVES: The use of more sensitive tests such as HCMV PCR or antigenemia may improve the outcome but probably will not eradicate all HCMV disease. Future possible strategies could include adoptive transfer of CD8+ HCMV-specific cytotoxic T lymphocytes clones derived from the donor marrow or boosting donor or patient immunity using subunit anti-HCMV vaccines such as gB or pp65.

Acyclovir↗

PubMed1998

Infections due to the herpesvirus group in immunocompromised patients.

Herpesvirus infections remain a significant cause of morbidity and mortality in iatrogenically immunosuppressed individuals despite the considerable progress achieved in recent years by the use of anti-viral drugs. Human cytomegalovirus is particularly important in this context and major advances have been made towards understanding the basis of cytomegalovirus latency and persistence. At the same time efforts continue to develop optimal virus detection in immunosuppressed individuals with a view to improving current therapeutic policies, and to define the emerging problem of anti-viral drug resistance. Finally, the evidence is gathering that the newest additions to the human herpesvirus family, i.e. human herpesviruses-6, -7 and -8, are significant pathogens in the immunosuppressed.

Journal Article↗

PubMed1998

Molecular epidemiology of two consecutive outbreaks of parainfluenza 3 in a bone marrow transplant unit.

Two consecutive nosocomial outbreaks of parainfluenza 3, in which 5 of 15 infected patients died, occurred in an adult bone marrow transplant unit. Parainfluenza 3 strain variation was assessed by reverse transcription-PCR sequencing of part of the parainfluenza 3 F gene, including the noncoding region, directly from clinical samples. Sequence data from the outbreaks were compared with those from 15 other parainfluenza 3 isolates circulating concurrently in the community; altogether, 13 strains which fell into three lineages were identified. Four immunosuppressed patients shed virus persistently for between 1 and 4 months without change in sequence. The first outbreak lasted 4 months and involved three parainfluenza 3 strains, and one persistently infected patient was implicated as the source of infection for three others. The second outbreak lasted for 1 month but involved only one strain. These data indicate that introduction of community parainfluenza 3 strains to the bone marrow transplant unit was followed by person-to-person transmission within the unit rather than reintroduction of virus from the community.

Adolescent↗

PubMed1997

Persistence of antibody to human parvovirus B19 after allogeneic bone marrow transplantation: role of prior recipient immunity.

Human parvovirus B19 (B19) IgG was studied retrospectively in 66 allogeneic bone marrow transplantation (BMT) patients using an enzyme-linked immunosorbent assay. Recipient and donor sera had been stored pre-BMT together with sequential sera thereafter. Approximately half of donors and recipients had anti-B19 IgG pre-BMT and thus the relative contributions of donor and recipient immunity to antibody production after transplantation could be assessed. For each patient, a serum taken 2 to 3 years after BMT was also tested and the results show that persistence of B19 antibody depends on prior recipient (P = .0003) but not on donor immunity (P = .8). The findings were similar in both sibling and (VUD) BMT volunteer unrelated donor patients. Analysis of sequential post-BMT sera from 41 of the patients, for whom appropriately timed samples were available, showed primary B19 infection in 3 seronegative individuals, whereas 5 others who were seropositive before BMT underwent recurrent infection. Sequential results from the remaining 33 patients without recent B19 infection showed no evidence for donor antibody transfer and confirmed that antibody persistence depends on prior recipient immunity. B19 IgG levels decreased variably with time and some patients eventually became seronegative. It is concluded that this long-term persistence of B19 antibody post-BMT is most probably due to the existence of long-lived recipient plasma cells.

Adult↗

PubMed1997

Chronic anemia due to parvovirus B19 infection in a bone marrow transplant patient after platelet transfusion.

BACKGROUND: Many reports document the transmission of human parvovirus B19 (B19) infection by clotting factor concentrates manufactured from large plasma pools. Transmission via other blood components originating from a single donor or a small number of donors, however, seems to occur only rarely. The study reported here identifies a B19 infection that was transmitted via a platelet donation. CASE REPORT: A multiply transfused allogeneic bone marrow transplant patient developed chronic anemia due to persistent B19 infection. The anemia responded to therapy with intravenous immunoglobulin. It was postulated that a transfusion was the source of the B19 infection. Archived sera from 90 implicated blood donors were tested for B19 IgM and DNA by the use of dot-blot hybridization and a nested polymerase chain reaction with primers from the B19 nonstructural gene. B19 DNA from patient and donor sera were sequenced. One of the 90 blood donors (Donor A) was B19 IgM positive and had a high level of B19 DNA. The patient was viremic 3 days after transfusion of platelets from this donor, and the sequence of B19 DNA from the patient exactly matched that of B19 DNA from the donor. A second blood donor (Donor B) had a low level of B19 DNA but was IgM negative. The patient showed no evidence of B19 infection after the transfusion of red cells from Donor B, and the sequence of this donor's B19 DNA was different from that in the patient. CONCLUSION: Blood Donor A with asymptomatic acute B19 infection was the source of B19 infection in the bone marrow transplant patient. Donor B with a low level of B19 DNA was not the source of infection.

Adult↗