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2.
S. Afr. j. obstet. gynaecol ; 19(3): 81-87, 2013.
Article in English | AIM (Africa) | ID: biblio-1270775

ABSTRACT

Objective.To describe the establishment of a colposcopy service at a district hospital in a rural sub-district of the Western Cape; South Africa; and assess its impact on colposcopy uptake. Design. A retrospective double-group cohort study using a laboratory database of cervical cytology results; clinical records and colposcopy clinic registers.Setting. The Overstrand sub-district; where 80 000 people are served by seven clinics and a district hospital in Hermanus; 120 km from its referral hospitals in Cape Town and Worcester. A colposcopy service was established at Hermanus Hospital in 2008.Subjects. All women in the sub-district who required colposcopy on the basis of cervical smears done in 2007 and 2009.Outcome measures. Numbers of women booked for colposcopy at distant referral hospitals in 2007 and at the district hospital in 2009; the proportions who attended colposcopy; the time from cervical smear to colposcopy; and comparison between the two years.Results. Uptake of colposcopy booked at distant referral hospitals was 67 in 2007. Uptake improved by 18 to 79 for the district hospital colposcopy service in 2009 (p=0.06). When patients from an area with no public transport to the district hospital were excluded from analysis; the improvement was more marked at 22 (p=0.02). The delay from cervical smear to colposcopy improved significantly from 170 to 141 days (p=0.02).Conclusion. Establishment of a colposcopy service in a rural sub-district increased uptake of colposcopy and decreased the delay from cervical smear to colposcopy. The service removed 202 booked patients in one year from the colposcopy load of the referral hospitals


Subject(s)
Ambulatory Care Facilities , Cervix Uteri , Colposcopy , Factor Analysis, Statistical , Hospitals , Vaginal Smears
3.
J Virol ; 83(19): 10234-44, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19605475

ABSTRACT

A broad Gag-specific CD8(+) T-cell response is associated with effective control of adult human immunodeficiency virus (HIV) infection. The association of certain HLA class I molecules, such as HLA-B*57, -B*5801, and -B*8101, with immune control is linked to mutations within Gag epitopes presented by these alleles that allow HIV to evade the immune response but that also reduce viral replicative capacity. Transmission of such viruses containing mutations within Gag epitopes results in lower viral loads in adult recipients. In this study of pediatric infection, we tested the hypothesis that children may tend to progress relatively slowly if either they themselves possess one of the protective HLA-B alleles or the mother possesses one of these alleles, thereby transmitting a low-fitness virus to the child. We analyzed HLA type, CD8(+) T-cell responses, and viral sequence changes for 61 mother-child pairs from Durban, South Africa, who were monitored from birth. Slow progression was significantly associated with the mother or child possessing one of the protective HLA-B alleles, and more significantly so when the protective allele was not shared by mother and child (P = 0.007). Slow progressors tended to make CD8(+) T-cell responses to Gag epitopes presented by the protective HLA-B alleles, in contrast to progressors expressing the same alleles (P = 0.07; Fisher's exact test). Mothers expressing the protective alleles were significantly more likely to transmit escape variants within the Gag epitopes presented by those alleles than mothers not expressing those alleles (75% versus 21%; P = 0.001). Reversion of transmitted escape mutations was observed in all slow-progressing children whose mothers possessed protective HLA-B alleles. These data show that HLA class I alleles influence disease progression in pediatric as well as adult infection, both as a result of the CD8(+) T-cell responses generated in the child and through the transmission of low-fitness viruses by the mother.


Subject(s)
HIV Infections/immunology , HIV Infections/pathology , HIV-1/metabolism , HLA Antigens/metabolism , CD8-Positive T-Lymphocytes/metabolism , Disease Progression , Epitopes , Female , Gene Products, gag/chemistry , HLA-B Antigens/metabolism , Humans , Infant , Infant, Newborn , Male , Mothers , Virus Replication
4.
AIDS Res Hum Retroviruses ; 24(2): 265-70, 2008 Feb.
Article in English | MEDLINE | ID: mdl-18284325

ABSTRACT

Multiple HIV-1-specific cytokine and proliferative responses by CD4(+) T cells have not been studied in acutely infected infants. Using an intracellular cytokine staining assay, 34 untreated clade C HIV-1-infected infants (2-102 days old) were assessed for IFN-gamma, 28/34 for IL-2, and 26/34 for TNF-alpha responses to all HIV-1 proteins. Responses were detected in 29%, 36%, and 15% of infants, respectively. Twelve of the original 34 infants were then studied longitudinally for 14 months to determine the effect of viral load on IFN-gamma Gag-specific responses: seven infants were treated for 1 year, stopped treatment, and resumed when CD4% was < 20 and five infants were treated only when the CD4% was <20. Following treatment cessation, there was an immediate increase in viral load followed by an increase in the magnitude of CD4(+) Gag-specific responses. Despite this, the majority of infants (54%) had to restart treatment by 24 months of age, indicating that the immune responses were antigen driven but not associated with protection. Among untreated infants HIV-specific CD4(+) responses were detected sporadically indicating a dysfunctional immune response in the face of constant exposure to high levels of viremia.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , HIV Infections/immunology , HIV-1/immunology , gag Gene Products, Human Immunodeficiency Virus/immunology , Animals , CD4 Lymphocyte Count , Cell Proliferation , Cells, Cultured , Humans , Infant , Interferon-gamma/biosynthesis , Interleukin-2/biosynthesis , Longitudinal Studies , Tumor Necrosis Factor-alpha/biosynthesis , Viral Load
5.
J Virol ; 81(23): 12775-84, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17881456

ABSTRACT

Human immunodeficiency virus (HIV)-infected infants in sub-Saharan Africa typically progress to AIDS or death by 2 years of life in the absence of antiretroviral therapy. This rapid progression to HIV disease has been related to immaturity of the adaptive immune response in infants. We screened 740 infants born to HIV-infected mothers and tracked development and specificity of HIV-specific CD8+ T-cell responses in 63 HIV-infected infants identified using gamma interferon enzyme-linked immunospot assays and intracellular cytokine staining. Forty-four in utero-infected and 19 intrapartum-infected infants were compared to 45 chronically infected children >2 years of age. Seventy percent (14 of 20) in utero-infected infants tested within the first week of life demonstrated HIV-specific CD8+ T-cell responses. Gag, Pol, and Nef were the principally targeted regions in chronic pediatric infection. However, Env dominated the overall response in one-third (12/36) of the acutely infected infants, compared to only 2/45 (4%) of chronically infected children (P = 0.00083). Gag-specific CD4+ T-cell responses were minimal to undetectable in the first 6 months of pediatric infection. These data indicate that failure to control HIV replication in in utero-infected infants is not due to an inability to induce responses but instead suggest secondary failure of adaptive immunity in containing this infection. Moreover, the detection of virus-specific CD8+ T-cell responses in the first days of life in most in utero-infected infants is encouraging for HIV vaccine interventions in infants.


Subject(s)
CD8-Positive T-Lymphocytes/immunology , HIV Infections/congenital , HIV Infections/immunology , T-Lymphocyte Subsets/immunology , Africa South of the Sahara , CD4-Positive T-Lymphocytes/immunology , Female , HIV/immunology , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Interferons/biosynthesis , Male , Pregnancy , Pregnancy Complications, Infectious , gag Gene Products, Human Immunodeficiency Virus/immunology , nef Gene Products, Human Immunodeficiency Virus/immunology , pol Gene Products, Human Immunodeficiency Virus/immunology
6.
AIDS ; 21(10): 1253-61, 2007 Jun 19.
Article in English | MEDLINE | ID: mdl-17545701

ABSTRACT

OBJECTIVES: To determine the natural history of HIV infection following peripartum single-dose nevirapine (sd-NVP) prophylaxis in a resource-limited country, and to assess implications for antiretroviral therapy (ART) roll-out programmes. METHODS: Infants of HIV-infected mothers in KwaZulu-Natal, South Africa, were tested on days 1 and 28 to detect intrauterine (IU) and intrapartum (IP) infection. Infant follow-up included monthly viral load and CD4 cell measurement. ART was initiated at infant CD4 cell% < or = 20%. RESULTS: In 740 infants born to 719 HIV-infected women, mother-to-child transmission (MTCT) was 10.3% (69% IU, 31% IP). Median viral load was higher in mothers of infants infected IP than IU (279 000 versus 86 600 copies/ml; P = 0.039) and lower in mothers of uninfected infants (median 26 750 copies/ml; P < 0.001). Peak viraemia was higher in infants infected IP than IU (5 160 000 versus 984 000 copies/ml; P < 0.001). Median viral load at birth in IU-infected infants (155 000 copies/ml) fell 1.4 log to 6510 copies/ml by day 5 and was beneath the detection limit using dried blood spot analysis in 38% of infants. CD4 cell% declined rapidly, to < or = 20% in 70% and < or = 25% in 85% [current World Health Organization (WHO) criteria for initiating ART] of infants by 6 months. CONCLUSIONS: MTCT was reduced by sd-NVP through an effect on IP transmission. Where MTCT occurred despite NVP, two-thirds of transmissions arose IU; IP-infected babies were born to mothers with very high viral load. Disease progression was particularly rapid, 85% infants meeting WHO criteria for ART within 6 months. These findings argue for more effective MTCT-prevention programmes in resource-limited countries.


Subject(s)
Anti-HIV Agents/administration & dosage , HIV Infections/immunology , Nevirapine/administration & dosage , CD4 Lymphocyte Count , Disease Progression , Drug Administration Schedule , Drug Therapy, Combination , Female , HIV Infections/epidemiology , HIV Infections/prevention & control , HIV-1/immunology , Humans , Infant , Infant, Newborn , Infectious Disease Transmission, Vertical , Morbidity , Mothers , Perinatal Care/methods , South Africa/epidemiology , Viral Load , Viremia/immunology
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