MATERNAL IMMUNE RESPONSES AND RISK OF INFANT INFECTION WITH HIV-1 AFTER A SHORT COURSE ZIDOVUDINE IN A COHORT OF HIV-1 INFECTED PREGNANT WOMEN IN RURAL KENYA

Objective: To investigate the effects of short-course nucleoside reverse transcriptaseinhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infantinfection with HIV-1 among rural-based mothers in western Kenya.Design: A prospective cohort study involving HIV-1 seropositive pregnant mothers andtheir infants.Subjects: One hundred and seven HIV-1 seropositive asymptomatic pregnant womenand their infants.Methods: After informed consent, the women were enrolled at gestation age between16-24 weeks. For cultural and economic reasons, all mothers were allowed to breastfeed their infants. Short-course antepartum regime of AZT was administered to allmothers starting at 36 weeks gestation until start of labour. Maternal absolute CD4+T cell subset assays were performed before 3rd trimester (about 36 weeks gestation)and after a 4-week therapy of AZT (at least one month post-nuptially). Infant HIV-1 status was determined by HIV-1 DNA polymerase chain reaction (PCR) on samplessequentially taken at 1, 2, 3, 4, 6 and 9 months and confirmed by serology at 18 monthsof age.Interventions: Antepartum short-course orally administered AZT: 300mg twice-dailystarting at 36 weeks gestation until start of labour, 300mg at labour onset and 300mgevery three hours during labour until delivery.Main Outcome Measures: Maternal CD4+ T cell counts before and after AZT treatment.Determination of infant HIV-1 infection status.Results: Among 107 women sampled, only 59 received full dose of AZT and thus qualifiedfor present analysis. Of these, 12 infected their children with HIV, while 47 did not.Comparison of CD4+ T cells before and after AZT treatment scored a significant risein all mothers (P = 0.01). This increase in CD4+ T cells was not significant amongmothers who infected their infants with HIV-1 (P = 0.474). However, a significant risein CD4+ T cells following AZT therapy was observed only in mothers who did nottransmit HIV-1 to their infants (P=0.014).Conclusion: These data suggest that a rise in the CD4+ T cell counts following shortAZT regimen, now widely in use in resource-weak countries, may be evidence of theactive suppression of the replication of HIV. However, further studies to examine themulti-factorial effect of CD4+ lymphocytes and pregnancy on MTCT of HIV need tobe carried out to help fully explain the effect of AZT on immune response and whetherthe CD4+T cell count can be used as a true test of immunological normalisation duringantiretroviral therapy

MEASLES TRENDS AND VACCINE EFFECTIVENESS IN NAIROBI, KENYA

ABSTRACTObjectives: To determine morbidity and mortality from measles and to estimate measlesvaccine effectiveness among children hospitalised with measles in two hospitals in Nairobi.Design: A review of hospital records (index cards).Setting: Kenyatta National Hospital and Mbagathi District Hospitals covering the years1996-2000.Method: A review of index cards for measles morbility and mortality was undertaken in thetwo hospitals. Measles data at the Kenya Expanded Programme on Immunisation coveringboth hospitals was analysed for vaccine effectiveness.Results: The incidence of measles was unusually high in 1998 between July and November(monthly range 130-305), reflecting on the occurrence of an outbreak at that time. There wasno definite monthly incidence trend of measles in 1996, 1997, 1999 and 2000. The median ageof cases was 13 months (range 0-420 months) for Kenyatta hospital and 18 months (range 1-336 months) for Mbagathi Hospital. Significantly, 29.8% of all cases were aged below ninemonths when routine immunisation for measles had not begun. The median number of daysspent in hospital were five days (range 0-87 days) for Kenyatta and four days (range 1-13days) for Mbagathi. The overall case fatality rate was 5.6% and was similar for both malesand females. The overall measles vaccine effectiveness among measles cases admitted toKenyatta and Mbagathi Hospitals was 84.1%.Conclusion: The case admissions in Kenyatta and Mbagathi Hospitals suggest measles wasprevalent in Nairobi over the latter half decade of the 1990’s. Apart from 1998 when therewas an outbreak, the seasonality of measles was dampened. The 1998 outbreak suggests abuild up of susceptible children the majority of whom were born in the last quarter of 1996.The high mortality may have had to do with the majority of cases presenting late whensymptoms were already complicated and severe

CD4T Lymphocyte subsets and disease manifestation in children with and without HIV born to HIV-1 infected mothers

Objective:To understand the natural history of HIV-1 infection in children in terms of evolution of childhood clinical manifestations versus the immune status, we prospectively studied children with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 for two years between March 1998 and March 2000. Design:A prospective cohort study. Setting:An institutional children's home. Subjects:Fifty nine children (26 males and 33 females) with and without maternally transmitted HIV-1 infection born to mothers infected with HIV-1 and adopted in institutional children home. Methods:HIV-1 status of children under nine months was confirmed by polymerase chain reaction (PCR). ELISA for HIV-1 antibody in serum/plasma was used to confirm HIV-infection status for children aged £18 months. Children were visited every three months between March and June 2000. At every visit blood was collected for total white cell count, haemoglobin and CD4+ and CD8+ T cell counts. The institutional doctor routinely examined children and treated all ailments. Clinical data were recorded. Measures: HIV-DNA, anti-HIV antibodies, total white blood count, total T cell counts, CD4 and CD8 T cell subset counts, frequency of childhood manifestations of infection. Results:The children were aged between 4.5 and 13 years. The baseline haematological and immunological profiles (mean, mode) were: HIV-1 sero-converters (WBC 7151,7150; HB 11.6, 12.0; CD4+ 686, 795; CD8+ 2168, 1507) and HIV-1 de-seroconverters (mean, mode) were: (WBC 8386, 7150; HB 11.7, 12.8; CD4+ 735, 795; CD8+ 2168, 1507). The commonest causes of illnesses among the HIV-1 children were URTI (85.3%), TB(56.1%), pneumonia (56.2%), tonsillitis (34.1%), parotiditis (28%) and acute otitis media (25%). The distribution of clinical manifestations was similar between the two categories of children, except URTI, whose prevalence was significantly increased among HIV-1 infected children (p-value=0.006). Among the HIV-1 infected children, only TB, parotiditis, and acute otitis media (AOM) were significantly associated with decreased CD4+ T cell count (

CD4T LYMPHOCYTE SUBSETS AND DISEASE MANIFESTATION IN CHILDREN WITH AND WITHOUT HIV BORN TO HIV-1 INFECTED MOTHERS

ABSTRACTObjective: To understand the natural history of HIV-1 infection in children in termsof evolution of childhood clinical manifestations versus the immune status, we prospectivelystudied children with and without maternally transmitted HIV-1 infection born tomothers infected with HIV-1 for two years between March 1998 and March 2000.Design: A prospective cohort study.Setting: An institutional children’s home.Subjects: Fifty nine children (26 males and 33 females) with and without maternallytransmitted HIV-1 infection born to mothers infected with HIV-1 and adopted ininstitutional children home.Methods: HIV-1 status of children under nine months was confirmed by polymerasechain reaction(PCR). ELISA for HIV-1 antibody in serum/plasma was used to confirmHIV-infection status for children aged £18 months. Children were visited every threemonths between March and June 2000. At every visit blood was collected for total whitecell count, haemoglobin and CD4+ and CD8+ T cell counts. The institutional doctorroutinely examined children and treated all ailments. Clinical data were recorded.Measures: HIV-DNA, anti-HIV antibodies, total white blood count, total T cell counts,CD4 and CD8 T cell subset counts, frequency of childhood manifestations of infection.Results: The children were aged between 4.5 and 13 years. The baseline haematologicaland immunological profiles (mean, mode) were: HIV-1 sero-converters (WBC 7151,7150;HB 11.6, 12.0; CD4+ 686, 795; CD8+ 2168, 1507) and HIV-1 de-seroconverters (mean,mode) were: (WBC 8386, 7150; HB 11.7, 12.8; CD4+ 735, 795; CD8+ 2168, 1507). Thecommonest causes of illnesses among the HIV-1 children were URTI (85.3%), TB(56.1%),pneumonia (56.2%), tonsillitis (34.1%), parotiditis (28%) and acute otitis media (25%).The distribution of clinical manifestations was similar between the two categories ofchildren, except URTI, whose prevalence was significantly increased among HIV-1infected children (p-value=0.006). Among the HIV-1 infected children, only TB,parotiditis, and acute otitis media (AOM) were significantly associated with decreasedCD4+ T cell count (p<0.05) resulting from HIV infection.Conclusions: HIV infection in children predisposes them to common childhood infectionsthat can be used as markers of immune decline. TB, AOM, URTI may be early indicatorsof suspicion that would enable selective screening for HIV infection in children

MATERNAL IMMUNE RESPONSES AND RISK OF INFANT INFECTION WITH HIV-1 AFTER A SHORT COURSE ZIDOVUDINE IN A COHORT OF HIV-1 INFECTED PREGNANT WOMEN IN RURAL KENYA

ABSTRACTObjective: To investigate the effects of short-course nucleoside reverse transcriptaseinhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infantinfection with HIV-1 among rural-based mothers in western Kenya.Design: A prospective cohort study involving HIV-1 seropositive pregnant mothers andtheir infants.Subjects: One hundred and seven HIV-1 seropositive asymptomatic pregnant womenand their infants.Methods: After informed consent, the women were enrolled at gestation age between16-24 weeks. For cultural and economic reasons, all mothers were allowed to breastfeed their infants. Short-course antepartum regime of AZT was administered to allmothers starting at 36 weeks gestation until start of labour. Maternal absolute CD4+T cell subset assays were performed before 3rd trimester (about 36 weeks gestation)and after a 4-week therapy of AZT (at least one month post-nuptially). Infant HIV-1 status was determined by HIV-1 DNA polymerase chain reaction (PCR) on samplessequentially taken at 1, 2, 3, 4, 6 and 9 months and confirmed by serology at 18 monthsof age.Interventions: Antepartum short-course orally administered AZT: 300mg twice-dailystarting at 36 weeks gestation until start of labour, 300mg at labour onset and 300mgevery three hours during labour until delivery.Main Outcome Measures: Maternal CD4+ T cell counts before and after AZT treatment.Determination of infant HIV-1 infection status.Results: Among 107 women sampled, only 59 received full dose of AZT and thus qualifiedfor present analysis. Of these, 12 infected their children with HIV, while 47 did not.Comparison of CD4+ T cells before and after AZT treatment scored a significant risein all mothers (P = 0.01). This increase in CD4+ T cells was not significant amongmothers who infected their infants with HIV-1 (P = 0.474). However, a significant risein CD4+ T cells following AZT therapy was observed only in mothers who did nottransmit HIV-1 to their infants (P=0.014).Conclusion: These data suggest that a rise in the CD4+ T cell counts following shortAZT regimen, now widely in use in resource-weak countries, may be evidence of theactive suppression of the replication of HIV. However, further studies to examine themulti-factorial effect of CD4+ lymphocytes and pregnancy on MTCT of HIV need tobe carried out to help fully explain the effect of AZT on immune response and whetherthe CD4+T cell count can be used as a true test of immunological normalisation duringantiretroviral therapy