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Biomedical subjects

E G Lyall

Publications and source records attributed to E G Lyall.

At least 19 recordsLinked to original sources
PubMed2001

Pneumocystis carinii pneumonia and cytomegalovirus infection in children with vertically acquired HIV infection.

OBJECTIVES: The outcome of Pneumocystis carinii pneumonia (PCP) in HIV-infected infants is poor, and the role of cytomegalovirus (CMV) co-infection in the course and outcome of PCP is unclear. This study describes the prevalence, clinical characteristics, management and changes in survival over time of vertically HIV-infected infants developing PCP and/or CMV infection. METHODS: Data on children with HIV, born in the UK and Ireland and reported to the National Study of HIV in Pregnancy and Childhood, with PCP and/or CMV were combined with clinical information collected from reporting paediatricians. RESULTS: By April 1998, 340 vertically HIV-infected children had been reported, of whom 93 had PCP and/or CMV, as their first AIDS indicator disease; 85 (91%) were infants. Among infants with PCP, 79% were born to mothers not diagnosed as HIV infected, and there was an independent and statistically significant association with breast-feeding, being black African, and developing CMV disease. Median survival after PCP and/or CMV was significantly better in those born between 1993 and 1998 compared with those born before 1993 (P = 0.009), and worse than after other AIDS diagnoses (P = 0.01). Infants with dual infection were more likely to be ventilated (P = 0.003) and receive corticosteroids (P = 0.002) than those with PCP alone. CONCLUSION: Although survival from PCP and CMV has improved over time, these remain serious and potentially fatal infections among infants in whom maternal HIV status is not recognized in pregnancy. Breast-feeding increases the risk of combined PCP and CMV infection, which is associated with severe disease.

AIDS-Related Opportunistic Infections↗
PubMed2001

Guidelines for the management of HIV infection in pregnant women and the prevention of mother-to-child transmission.

AIMS OF THE GUIDELINES: These guidelines, drawn up by a multidisciplinary group of clinicians and lay workers active in the management of pregnant women infected with HIV, aim to give up-to-date information on interventions to reduce the risk of mother to child transmission of the virus. The evidence on the use of interventions to prevent mother to child transmission of HIV has been graded according to the strength of the data as per the definitions of the US Agency for Health Care Policy and Research [1]. Weighted evidence on the use of combination antiretroviral therapy (ART) for the treatment of HIV infection per se is presented in the BHIVA guidelines for adults [2,3]. The highest level evidence (i.e. randomised controlled trials (RCTs) or large, well conducted meta-analyses) is only available for formula feeding, prelabour caesarean section and zidovudine monotherapy. The need to treat mothers for HIV infection has led to the widespread use of ART in pregnancy which in turn results in new questions such as how to deliver when the mother, on therapy, has no detectable plasma viraemia with the most sensitive assays. In addressing many common and/or difficult clinical scenarios in the absence of 'best evidence' the guidelines rely heavily on 'expert opinion'. Recommendations for management are given in the section on clinical scenarios, and summarized in Table 3. An expanded version of these guidelines with an appendix on safety and toxicity data is available on the BHIVA website http://www.bhiva.org. The authors are available to discuss individual cases.

Adult↗
PubMed2000

Pharmacological implications of lengthened in-utero exposure to nevirapine.

Given as a single dose to the mother during labour, nevirapine can protect the neonate from HIV-1 infection for up to 7 days. However, after maternal nevirapine therapy during pregnancy, neonatal plasma concentrations of nevirapine decline more rapidly, suggesting in-utero liver enzyme induction.

Anti-HIV Agents↗
PubMed2000

Management of HIV and pregnancy in England's North Thames Region 1999: a survey of practice in 21 hospitals.

OBJECTIVES: To ascertain current practices in the diagnosis and management of HIV and pregnancy in the North Thames Region. METHODS: Postal survey using a self-completed questionnaire sent to the head of all of the Region's 34 units involved in the care of HIV. The survey asked questions on current policy around HIV and pregnancy in the HIV units and associated antenatal clinics and was linked to a case-note survey of pregnant, HIV-positive women in the last 2 years. RESULTS: Over 50% of the responding antenatal units recommended the HIV test by March 1999. Most HIV units were offering a range of antiretroviral regimens in pregnancy, although a minority (33%) did not offer triple therapy. Elective Caesarean section was the recommended mode of delivery for most women (90%) irrespective of drug therapy or viral load. Most infants were being tested for HIV infection by a combination of PCR, viral culture and antibody testing to 18 months of age. All the infants (19) followed to 6 months of age in the case-note survey were PCR negative. Reporting rates to the National Survey of HIV in Pregnancy were high (87%) but poor for the Drug Exposure Register (33%). CONCLUSIONS: Management of HIV and pregnancy in the North Thames units showed a large amount of consistency with regard to testing policies and management. However, there were a few units that did not offer therapy appropriate for advanced disease despite the recommendations of national bodies and a few units still did not recommend HIV testing to all women.

England↗
PubMed1999

Mother to infant transmission of HIV.

Mother-to-infant transmission is the route by which the vast majority of children acquire HIV. Several refinements in our understanding in how to reduce the risk of transmission have been made in the past year. The risks from prolonged breast feeding, and the protective effects of caesarean section have been clarified. Shorter interventions using antiretroviral drugs are useful in resource-constrained settings. In developed countries, combination antiretroviral therapies to reduce maternal viral loads to below limits of detection are being explored, but there is concern about toxicity particularly of indinavir in pregnancy. Combining interventions can reduce transmission rates to less than 2%.

Journal Article↗
PubMed1999

Evidence for horizontal and not vertical transmission of human herpesvirus 8 in children born to human immunodeficiency virus-infected mothers.

A survey of antibody responses to human herpesvirus 8 (HHV-8) was undertaken to examine the mode of transmission of this virus to children born to mothers with HIV. Methods. Serum samples from a cohort of 92 mother-infant pairs and a cross-sectional cohort of 100 children (median age, 4 years) were tested. In the cohort of mother-infant pairs, 14 infants were HIV-infected, 72 were not and the HIV status was unknown for 6. In the cohort of children 70 were HIV-infected and 30 were vertically exposed but uninfected. Serologic responses to two HHV-8 antigens, latency-associated nuclear antigen and the structural antigen encoded by open reading frame 65 were detected by immunofluorescent antibody test and enzyme-linked immunoassay. Results were confirmed by Western blot. Results. All HHV-8-seropositive mothers were African (17 of 92, 18.5%). Six of their infants were HHV-8-seronegative and 11 had at least 1 HHV-8-seropositive sample. One of the 11 infants tested only at birth had a lower antibody titer than the mother; the remaining 10 infants had decreasing titers up to 7 months of age and 6 became seronegative. No infants born to HHV-8-seronegative mothers had antibodies to the virus. The seroprevalence to HHV-8 was 6% in the cohort of children. All had African mothers and their median age was greater than that of the cohort (8.4 vs. 4.0 years). Five were coinfected with HIV. Conclusions. HHV-8 was not vertically transmitted by any of the HIV-coinfected mothers. Acquisition of antibody to HHV-8 occurred in older children, implying a horizontal route of transmission.

Adult↗
PubMed1999

British HIV Association guidelines for prescribing antiretroviral therapy in pregnancy (1998).

The aim of antiretroviral therapy in pregnancy is to deliver a healthy uninfected child to a healthy mother, without prejudicing the future treatment opportunities of the mother. The use of zidovudine monotherapy rapidly became standard practice once it had been shown to reduce by 67% mother to child transmission in women with CD4+ lymphocyte counts above 200 x 10(6)/l. High rates of transmission are seen when maternal disease is advanced (high viral load, low CD4+ lymphocyte counts) despite zidovudine. In these women highly active antiretroviral therapy gives the best prospect for prolonged health and it is anticipated that reducing plasma viral load below the limits of detection will further reduce transmission rates. However, safety data for antiretroviral therapy in pregnancy are limited and each additional treatment exposes a significant proportion of uninfected infants to potential long term hazards. Where maternal therapy is not indicated and the sole objective of treatment is to reduce mother to child transmission, recent data suggest that short course zidovudine (especially in conjunction with prelabour caesarean section) is a reasonable option. This may minimise the emergence of viruses with reduced sensitivity to zidovudine and preserve maternal options for later therapy.

Anti-HIV Agents↗
PubMed1998

Review of uptake of interventions to reduce mother to child transmission of HIV by women aware of their HIV status.

OBJECTIVES: To examine the change in uptake of interventions to reduce transmission of HIV from mothers to infants from January 1994 to July 1997. DESIGN: Review of mother-infant pairs who presented for infant diagnosis of HIV infection. SETTING: Central London hospital with facilities for diagnosis of infant HIV infection. SUBJECTS: 57 consecutive mother-infant pairs, mainly from central London but also referred from surrounding hospitals. INTERVENTIONS: Data were collected on mother's country of origin; CD4 count at delivery; plasma HIV RNA copies/ml; mode of delivery; antiretroviral therapy; infant feeding; and HIV infection in infants. MAIN OUTCOME MEASURES: HIV infection of infants. RESULTS: The vertical transmission rate was 12% (7 pairs; 95% confidence interval 3% to 22%). All mothers chose not to breast feed. The caesarean section rate was 53% (30/57). Antiretroviral therapy was taken by 68.5% (39/57) of mother-infant pairs. With antiretroviral therapy or caesarean section, or both, transmission occurred in 6% (0% to 13%) of pairs (3/50). During the 24 months of 1994 and 1995, 21% (4/19) of infants were infected with HIV; 7.9% (3/38) were infected over the 19 months January 1996 to July 1997. The caesarean section rate did not change over these periods. Use of antiretroviral therapy increased from 31.5% (6/19) to 86.8% (33/38) (P < 0.0001). CONCLUSION: Women with a diagnosis of HIV infection acted to reduce the risk of transmission to their infants. Uptake of antiretroviral therapy increased significantly over time, and the caesarean section rate was persistently high.

Africa↗
PubMed1998

Intrapartum mucosal exposure to human immunodeficiency virus type 1 (HIV-1) of infants born to HIV-1-infected mothers correlates with maternal plasma virus burden.

The majority of vertical infections with human immunodeficiency virus type 1 (HIV-1) occur at or near delivery, strongly suggesting a mucosal route of transmission. The frequency and level of intrapartum mucosal exposure to HIV-1 of 22 infants born to infected mothers was investigated. Maternal plasma HIV-1 RNA and CD4 cell count were measured at delivery. Infant oropharyngeal aspirates obtained at birth were examined for HIV-1 RNA by reverse transcription-polymerase chain reaction and qualitative nucleic acid sequence-based amplification. Nine infants (41%) had detectable levels of HIV-1 RNA, 3 of which were quantifiable (mean, 3000 copies/mL). This mucosal exposure to HIV-1 during delivery did not lead to infection of any infant. Cesarian delivery did not reduce mucosal exposure to HIV-1. Mucosal exposure did not correlate with maternal CD4 cell count but did correlate with maternal plasma virus load and was reduced by antiretroviral therapy.

Adult↗
PubMed1997

Response to influenza virus vaccination in vertical HIV infection.

OBJECTIVE: To assess the antibody response to influenza vaccine of children vertically infected with HIV. DESIGN: Prospective study in HIV infected children vaccinated during the winter of 1994-5. SETTING: Family HIV clinic at St Mary's Hospital, Paddington. SUBJECTS: 25 children, aged 1-11 years, vertically infected with HIV. MAIN OUTCOME MEASURES: Responses to influenza antigens (H1N1-A/Taiwan/1/86, H3N2-A/Shandong/9/93, B/Panama/45/ 90) were tested by haemagglutination inhibition. Antibody responses were assessed according to clinical symptoms and immune function, stratified according to the 1994 revised classification for HIV infection in children. RESULTS: 23 children (92%) had either very low or no detectable antibody before vaccination. New protective antibody responses were made by 10 children (40%): in seven to a single antigen, in two to two antigens, and in one to all three antigens. For each antigen there was an overall small increase in the mean geometric titre of antibody produced, but this only reached a protective level for antigen H1N1 and for children with minimal symptoms. Less symptomatic children were significantly more likely to produce a protective antibody response to influenza vaccination. No association was found between immune function, as measured by CD4 count, and vaccine response. CONCLUSIONS: Only vaccination of the least symptomatic HIV infected children against influenza is likely to be effective. This will not only protect them against influenza, but will also protect other more immunosuppressed and vulnerable members of their families.

Antibodies, Viral↗
PubMed1995

Human herpesvirus-6 DNA in the saliva of paediatric oncology patients and controls.

Children with malignancy are immunosuppressed and susceptible to serious infections with herpesviruses. The majority of children on chemotherapy for malignancy are seropositive for human herpesvirus-6 (HHV-6), and although HHV-6 has been demonstrated to be a pathogen in severely immunocompromised patients, whether this is the case for paediatric oncology patients is unknown. HHV-6 is secreted in saliva and in this study samples were examined prospectively for HHV-6 DNA in healthy children and those with malignancy. In a nested polymerase chain reaction (PCR), a 287 bp outer fragment and 163 inner fragment of HHV-6 DNA were amplified. The resulting amplimer contained a Hind III restriction site present only in "B" type HHV-6 and this was used to identify the type of HHV-6 amplified. In saliva from healthy control children, 74% (28/38) of samples were HHV-6 DNA-positive in either the supernate, pellet or both. In the patients, 58% (45/77) of all samples were HHV-6 DNA-positive. When sequential samples from twelve patients were examined the children appeared to fall into two groups: those who were frequently HHV-6 DNA-positive (60% of samples or more) and those who were rarely HHV-6 DNA-positive (33% of samples or less) (P < 0.0001). The only apparent difference between these two groups was that the less frequently HHV-6-positive group was more often febrile and unwell with neutropaenia. Hind III digestion demonstrated all the positive samples to be "B" type HHV-6. Possible explanations for this difference in HHV-6 secretion between the patient groups are discussed.

Adolescent↗
PubMed1994

Serological response of paediatric oncology patients to human herpesvirus-6.

The serological response of paediatric oncology patients to human herpesvirus-6 (HHV-6) was investigated at presentation and during treatment. Sera from 66 patients presenting with malignancy and 66 controls were examined for anti-HHV-6 IgG by indirect immunofluorescence test (IFA) and enzyme linked immunosorbent assay (ELISA), and for anti-HHV-6 IgM by IFA. Serial samples from 45 children on chemotherapy were examined for anti-HHV-6 IgG by ELISA and sera from selected patients on chemotherapy were examined for IgM by IFA. The response of these patients to four other herpesviruses was also investigated. Ninety percent of presenting patients and controls were IgG positive for HHV-6 by IFA and ELISA. Anti-HHV-6 IgG as measured by the HHV-6 ELISA index declined over time in patients on chemotherapy. Two presenting controls and one leukaemic child with a primary cytomegalovirus seroconversion were anti-HHV-6 IgM positive. In the patient group seropositivity to herpesviruses (types 1-6) increased with age, the mean age of those with IgG to HHV-6 alone was 3.7 years compared to 6.8 years for those with antibodies to all five viruses. At the time of presentation paediatric oncology patients have a similar serological response to HHV-6 as age-matched controls and this IgG response wanes with treatment. Whether this is significant in terms of viral pathogenicity is not known and will require investigation of viral activity in these patients.

Age Factors↗
PubMed1994

Acyclovir resistant varicella zoster and HIV infection.

A child infected with HIV who developed chronic varicella zoster virus infection resistant to acyclovir is presented. The clinical course of the infection, treatment, virological investigations, and relationship of the infection to the child's immunodeficient state are discussed.

AIDS-Related Opportunistic Infections↗