PubMed Health⌕ Search

Biomedical subjects

D M Gibb

Publications and source records attributed to D M Gibb.

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↗
PubMed2000

Mother-to-child transmission of hepatitis C virus: evidence for preventable peripartum transmission.

BACKGROUND: Little information is available about the timing of mother-to-child transmission of hepatitis C virus (HCV), and no interventions to decrease transmission rates have been identified. We examined the effect of risk factors, including mode of delivery, on the vertical transmission rate. METHODS: Data from HCV-infected women and their infants from three hospitals in Ireland and from a British Paediatric Surveillance Unit study of infants born to HCV-infected mothers were used to estimate the vertical transmission rate and risk factors for transmission. We used a probabilistic model using methods that simultaneously estimated the time to HCV-antibody loss in uninfected infants and the diagnostic accuracy of PCR tests for HCV RNA. FINDINGS: 441 mother-child pairs from the UK (227) and Ireland (214) were included. 50% of uninfected children became HCV-antibody negative by 8 months and 95% by 13 months. The estimated specificity of PCR for HCV RNA was 97% (95% CI 96-99) and was unrelated to age; sensitivity was only 22% (7-46) in the first month but rose sharply to 97% (85-100) thereafter. The vertical transmission rate was 6.7% (4.1-10.2) overall, and 3.8 times higher in HIV coinfected (n=22) than in HIV-negative women after adjustment for other factors (p=0.06). No effect of breastfeeding on transmission was observed, although only 59 women breastfed. However, delivery by elective caesarean section before membrane rupture was associated with a lower transmission risk than vaginal or emergency caesarean-section delivery (odds ratio 0 [0-0.87], p=0.04, after adjustment for other factors). INTERPRETATION: The low sensitivity of HCV RNA soon after birth and the finding of a lower transmission rate after delivery by elective caesarean section suggest that HCV transmission occurs predominantly around the time of delivery. If the findings on elective caesarean section are confirmed in other studies, the case for antenatal HCV testing should be reconsidered.

Age Factors↗
PubMed2000

Immune repopulation after HAART in previously untreated HIV-1-infected children. Paediatric European Network for Treatment of AIDS (PENTA) Steering Committee.

In 25 vertically HIV-infected children receiving highly-active antiretroviral therapy, a 3-log10 reduction in plasma HIV RNA load was maintained for 1 year and was associated with a doubling of the CD4-cell percentage. Most (75%) new CD4 cells carried the CD45RA marker of naive cells and there was only a small rise in memory cells (CD45RO). This pattern of immune restoration differs from adults, and may be due to the presence of a functioning thymus in children.

Anti-HIV Agents↗
PubMed2000

Active surveillance of hepatitis C infection in the UK and Ireland.

AIM: To investigate the prevalence, distribution, and clinical details of paediatric hepatitis C virus (HCV) infection in the UK and Ireland. METHODS: Active monthly surveillance questionnaire study coordinated through the British Paediatric Surveillance Unit, to all consultant paediatricians in 1997 and 1998. RESULTS: A total of 182 HCV infected children were reported from 54 centres and by paediatricians from eight different specialties. In 40 children HCV was acquired through mother to child transmission (MTC children); 142 were infected by contaminated blood products (n = 134), organ transplantation (n = 2), needles (n = 4), or unknown risk factor (n = 2). Intravenous drug use was the risk factor for 35 mothers of MTC children. Twelve children were coinfected with HIV and four with HBV. Recent serum aspartate aminotransferase or alanine aminotransferase values were at least twofold greater than the upper limit of normal in 24 of 152 children; this occurred in five of 11 HIV coinfected children. Liver histology, available in 53 children, showed normal (7%), mild (74%), moderate (17%), or severe (2%) hepatitis. Twenty eight children had received therapy with interferon alfa. CONCLUSION: Most current paediatric HCV infection in UK and Ireland has been acquired from contaminated blood products, and most children are asymptomatic. There is a need for multicentre trials to inform clinical practice and development of good practice guidelines in this area. Long term follow up of this cohort of HCV infected children is planned to help determine the natural history over the long term of HCV acquired during infancy and childhood.

Child↗
PubMed2000

Economic issues in the prevention of vertical transmission of HIV.

In the absence of interventions, 20% of infants born to women infected with HIV acquire infection from their mother at or before delivery. A further 15% are infected through breast feeding. Prenatal testing for HIV allows infected women to be reliably identified so that they can receive antiretroviral therapy and, in countries with safe water supplies, be advised not to breast feed. These and other interventions can reduce the risk of transmission to 5% or less. Economic evaluations of prenatal testing for HIV are reviewed and compared in this article, and future research priorities outlined. These studies set the costs of testing and intervention against the averted lifetime costs of paediatric infection, and generate estimates of the HIV prevalence threshold above which there would be a net cost saving, or calculate the cost per life-year saved given a particular prevalence. In the developed world, prenatal testing has been adopted in many countries, and recent economic analyses broadly support this. Future research is likely to focus on the incremental benefits of different antiretroviral regimens in lowering transmission rates still further, with or without elective caesarean section, and the possibility that some may lead to adverse effects in uninfected infants exposed to them in utero. Some earlier assessments in resource-poor settings concluded that prenatal testing was unaffordable or of doubtful cost effectiveness. This negative conclusion appears to be the result of very low estimates of the lifetime costs of paediatric HIV infection, together with developed world conceptions of pre-test counselling. The demonstration that nevirapine reduces transmission risk at a low cost has transformed the outlook, and there is hope that antiretrovirals can act prophylactically to prevent infection of the breast-fed child. However, to achieve a sustained reduction in vertical transmission there may be a need to evaluate the need for a strengthened infrastructure to deliver prenatal HIV testing and treatment, as well as programmes to reduce HIV incidence in adults.

HIV Infections↗
PubMed1999

Vertical transmission rates for HIV in the British Isles: estimates based on surveillance data.

OBJECTIVE: To estimate and interpret time trends in vertical transmission rates for HIV using data from national obstetric and paediatric surveillance registers. DESIGN: Prospective study of HIV infected women reported through obstetric surveillance. HIV infection status of the child and onset of AIDS were reported through paediatric surveillance. Rates of vertical transmission and progression to AIDS rate were estimated by methods that take account of incomplete follow up of children with indeterminate infection status and delay in AIDS reporting. SETTING: British Isles. SUBJECTS: Pregnant women infected with HIV whose infection was diagnosed before delivery, and their babies. MAIN OUTCOME MEASURES: Mother to child transmission of infection and progression to AIDS in children. RESULTS: By January 1999, 800 children born to diagnosed HIV infected women who had not breast fed had been reported. Vertical transmission rates rose to 19.6% (95% confidence interval 8. 0% to 32.5%) in 1993 before falling to 2.2% (0% to 7.8%) in 1998. Between 1995 and 1998 use of antiretroviral treatment increased significantly each year, reaching 97% of live births in 1998. The rate of elective caesarean section remained constant, at around 40%, up to 1997 but increased to 62% in 1998. Caesarean section and antiretroviral treatment together were estimated to reduce risk of transmission from 31.6% (13.6% to 52.2%) to 4.2% (0.8% to 8.5%). The proportion of infected children developing AIDS in the first 6 months fell from 17.7% (6.8% to 30.8%) before 1994 to 7.2% (0% to 15. 7%) after, coinciding with increased use of prophylaxis against Pneumocystis carinii pneumonia. CONCLUSIONS: In the British Isles both HIV related morbidity and vertical transmission are being reduced through increased use of interventions.

Acquired Immunodeficiency Syndrome↗
PubMed1999

Cost effectiveness analysis of antenatal HIV screening in United Kingdom.

OBJECTIVE: To assess the cost effectiveness of universal antenatal HIV screening compared with selective screening in the United Kingdom. DESIGN: Incremental cost effectiveness analysis relating additional costs of screening to life years gained. Maternal and paediatric costs and life years were combined. SETTING: United Kingdom. MAIN OUTCOME MEASURES: Number of districts for which universal screening would be cost effective compared with selective screening under various conditions. RESULTS: On base case assumptions, a new diagnosis of a pregnant woman with HIV results in a gain of 6.392 life years and additional expenditure of 14 833 pounds. If decision makers are prepared to pay up to 10 000 pounds an additional life year, this would imply a net benefit of 49 090 pounds (range 12 300 pounds- 59 000 pounds), which would be available to detect each additional infected woman in an antenatal screening programme. In London, universal antenatal screening would be cost effective compared with a selective screening under any reasonable assumptions about screening costs. Outside London, universal screening with uptake above 90% would be cost effective with a 0.60 pounds HIV antibody test cost and up to 3.5 minutes for pretest discussion. Cost effectiveness of universal testing is lower if selective testing can achieve high uptake among those at higher risk. A universal strategy with only 50% uptake may not be less cost effective in low prevalence districts and may cost more and be less effective than a well run selective strategy. CONCLUSIONS: Universal screening with pretest discussion should be adopted throughout the United Kingdom as part of routine antenatal care as long as test costs can be kept low and uptake high.

Anti-HIV Agents↗
PubMed1999

Costs and benefits to the mother of antenatal HIV testing: estimates from simulation modelling.

OBJECTIVE: To assess the health service costs and benefits for the woman of an earlier HIV diagnosis as a result of antenatal HIV testing. DESIGN: A model of maternal disease progression was developed based on the rate of decline in CD4 cell counts and applied to two matched simulated cohorts of women with identical initial CD4 cell levels and decline rates but whose HIV diagnosis occurred at different times as a result of antenatal HIV testing. UK data on CD4 cell count at HIV diagnosis and annual health service costs of care excluding antiretroviral therapy (ART) incurred at defined states of CD4 cell count were taken from published UK data. Costs of triple ART were added and effectiveness modelled by retarding the rate of CD4 cell count decline. Discounting costs at 6% and life-years at 2% per year, the additional costs per life-year gained by screening were calculated. Uncertainty was explored using sensitivity analysis. RESULTS: Costs per life-year gained by antenatal diagnosis of women were pound sterling 51258 ($76887) assuming untested women were diagnosed a median of 20.4 months later than tested women, ART was initiated at a CD4 cell count of 350x10(6) cells/l and ART efficacy retarded decline in CD4 cell counts by 40% for life. Sensitivity analyses showed results were most sensitive to the assumed efficacy of lifetime ART and time assumed to HIV diagnosis for women not tested in pregnancy. CONCLUSION: This model provides a way of estimating the additional costs and benefits of future care for the woman resulting from an earlier HIV diagnosis through antenatal testing. These should be included with the paediatric costs averted and life-years gained from interventions to reduce mother-to-child transmission in order to evaluate the cost-effectiveness of antenatal screening in different populations and settings.

CD4 Lymphocyte Count↗
PubMed1999

Selective versus universal antenatal HIV testing: epidemiological and implementational factors in policy choice.

OBJECTIVE: To develop an epidemiological basis for economic analyses of selective and universal antenatal screening strategies, and to apply it to the UK. METHODS: The prevalence of higher-risk women and the prevalence of undiagnosed infection within groups of high-risk and low-risk women was estimated from surveillance and survey data. The numbers of women tested and the numbers of infected women who would be identified by universal and selective strategies were then calculated under a range of assumptions about the identification of higher-risk women and acceptance of testing. RESULTS: In higher-risk women estimated prevalence of undiagnosed infection was between 0.06% and 2.8%, comparing well with independent estimates. In low-risk women, estimates ranged from 0.014% in London to 0.002% in the rest of the UK. If uptake among the high-risk women was the same in selective and universal strategies, universal testing would entail testing between 7100 (London) and 50000 (rest of England) additional women to detect an additional case. However, if selective screening identified only 60% of those at high risk and achieved only 60% acceptance compared with a universal programme, then universal screening would require only 1150 additional women to identify one additional case in London, compared to 6470 in Scotland and 13140 in the rest of the UK. CONCLUSIONS: Overall prevalence does not form an adequate basis for determining screening strategy. Instead, universal screening can be justified either because the prevalence of HIV in the low-risk group is sufficiently high, or because it achieves sufficiently higher uptake relative to selective screening among those at higher risk.

Female↗
PubMed1998

Factors affecting uptake of antenatal HIV testing in London: results of a multicentre study.

OBJECTIVES: To measure the uptake of antenatal HIV testing and determine its relation to risk of HIV and to screening practices. DESIGN: Multicentre prospective questionnaire study. SUBJECTS: Pregnant women attending six maternity units. SETTING: Inner London, 1995-6. MAIN OUTCOME MEASURES: Uptake of testing by risk factors for HIV, ethnicity, and factors about the antenatal interview. RESULTS: All units had a "universal offer" policy for HIV testing. In five units forms were completed for 18,791 (88%) of 21,247 pregnant women. The sixth unit, where the response rate was too low to assess uptake, was excluded from the analysis. Uptake ranged from 3.4% to 51.2% (overall 22.9%), in parallel with detection of previously undiagnosed infection in pregnant women (4.9-60%). Controlling for unit, uptake was higher among the 7% who disclosed risk factors. Among those at low risk, uptake varied by ethnic group (South Asian women 9%; Latin American and Mediterranean women 33%). The relation between uptake and HIV risk category varied greatly across units. Despite increased HIV seroprevalence in black African women, uptake was similar in this group to that among women at low risk (24%). Uptake increased 2.1-fold if HIV transmission was discussed. Midwives reported spending 7 (2-15) minutes discussing HIV issues. CONCLUSIONS: Uptake of HIV testing was unacceptably low in all units, with maternity unit the strongest predictor. New approaches to antenatal HIV testing are urgently required and uptake should be audited routinely.

Africa↗
PubMed1998

Cervical length at 23 weeks of gestation: the value of Shirodkar suture for the short cervix.

OBJECTIVE: To examine the possible benefit of cervical cerclage in women with a very short cervix identified during routine sonographic assessment of cervical length at 23 weeks of gestation. METHODS: Transvaginal sonography was used to measure cervical length at 23 weeks of gestation in 2702 women with singleton pregnancies attending for routine antenatal care. In 43 (1.6%) cases the cervical length was < or = 15 mm. The 43 women in this group were referred to their obstetricians for the further management of pregnancy; in 21 cases, the pregnancy was managed expectantly and in 22 a Shirodkar suture was inserted under spinal anesthesia. The two groups were compared in terms of patient characteristics and pregnancy outcome. RESULTS: The 22 patients that were treated with cervical cerclage were not significantly different from the 21 given expectant management in ethnic origin, ponderal index, cigarette smoking or past obstetric history. The median cervical length was 10 mm in both groups. In the cervical cerclage group, 21 delivered after 32 weeks and one (5%) had spontaneous onset of labor and delivery before 32 completed weeks; all 22 infants survived. In the expectant management group, 11 (52%) had spontaneous onset of labor and delivery before 32 weeks; 20 infants survived but one baby died in the neonatal period. CONCLUSIONS: In women with a cervical length of < or = 15 mm at 23 weeks there is a more than 50% chance of spontaneous delivery at less than 32 weeks. Insertion of a Shirodkar suture in women with a very short cervix may be associated with a ten-fold reduction in risk for such early delivery.

Cervix Uteri↗
PubMed1998

Performance of antenatal HIV screening strategies in the United Kingdom.

BACKGROUND: In 1996 only 13.5% of previously undiagnosed HIV infected women were detected in pregnancy. In this study, all 265 maternity units in the United Kingdom were surveyed to determine the relation between screening strategy, uptake of testing, and detection rate. METHODS: Data on HIV screening strategy and uptake of testing were collected in 1997 by postal questionnaire. The proportion of women with previously undiagnosed HIV infection identified during pregnancy (detection rate) was calculated using data from national obstetric HIV surveillance and unlinked anonymous seroprevalence studies. RESULTS: 239 (90%) units responded; 25 of these (10%) had a universal offer strategy, 89 (37%) a selective offer, and 125 (52%) tested only women who requested it. All selective units offered testing to injecting drug users, but only 26% to women who had lived abroad in high prevalence areas. Uptake was over 10% in only eight units, all with a universal strategy, and in 76% of selective units it was below 0.1%. The detection rate was 14.7% in universal units, 7.8% in selective units, and 7.7% in on request units. In universal units, detection increased by 6.3% (95% confidence interval 3.7% to 8.8%) for every 10% increase in uptake of testing. There was evidence of both selective presentation for testing and avoidance of testing among infected women. CONCLUSIONS: All current antenatal HIV testing strategies fail to identify most infected women. Universal offer strategies achieve a very low uptake and a poor detection rate. Units with selective strategies tend to test only a minority of women at high risk and do not target all the main high risk groups.

Female↗
PubMed1997

Uptake of interventions to reduce mother-to-child transmission of HIV in the United Kingdom and Ireland.

OBJECTIVES: To describe the uptake of interventions to reduce mother-to-child transmission of HIV infection. DESIGN: Voluntary confidential reporting of HIV infection in pregnancy and childhood; telephone interview with key professionals in all London maternity units. SUBJECTS AND SETTING: HIV-infected pregnant women and children in the United Kingdom and Ireland. MAIN OUTCOME MEASURES: Trends in breastfeeding, use of zidovudine, mode of delivery and terminations of pregnancy. RESULTS: Between 1990 and 1995, 14 (4%) out of 314 women diagnosed with HIV infection before delivery breastfed compared with 109 (77%) out of 142 diagnosed after delivery. Since 1994, zidovudine use has increased in each 6-month period (14, 39, 67, and 75%; chi 2 = 17.5, P < 0.001), although in 1995 it was the policy of only 48% of London maternity units to offer zidovudine to HIV-infected women. During 1995, 44% of HIV-infected women were delivered by elective Cesarean section. Since 1990, 20% of women first diagnosed in pregnancy were reported to have their pregnancy terminated. CONCLUSIONS: Although detection of previously undiagnosed HIV infection in pregnancy remains low in the United Kingdom, and particularly in London, HIV-infected pregnant women who are aware of their status are increasingly active in taking up interventions to reduce transmission to their infants. If all HIV-infected women attending for antenatal care in London consented to testing and took up interventions and termination of pregnancy at the rates observed in this study, the number of vertically infected babies born in London each year could be reduced from an estimated 41 to 13.

Abortion, Induced↗
PubMed1997

Malignancies in UK children with HIV infection acquired from mother to child transmission.

By April 1995, 302 cases of vertically acquired HIV infection had been reported through the British Paediatric Association Surveillance Unit. Over 50% of these children had developed an AIDS indicator disease, including nine malignancies (seven cases of non-Hodgkin's lymphoma (NHL) and two of Kaposi's sarcoma). There were two other malignancies that were not AIDS indicator diseases. In children less than 5 years of age the incidence of NHL was approximately 2500 times greater than expected in the UK child population. Three children presented with NHL as their AIDS indicator disease and four developed NHL at a median of 14 (range 10-19) months after the initial diagnosis of AIDS. Six of the seven children died at a median of 6.5 (range 2-14) months after the diagnosis of NHL. The seventh child responded to treatment and is alive nearly four years later. Histology was available in five cases, of which four were of B cell and one of T cell origin. Epstein-Barr virus was detected in all three patients with NHL where it was sought; all had B cell lymphomas. Although comparatively rare, malignancies occur in children infected with HIV and may be the presenting illness. Paediatricians now need to consider HIV infection as a predisposing cause of childhood cancer, especially NHL.

Child, Preschool↗