3. Electronic Theses and Dissertations (ETDs) - All submissions
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Item Development of the routine laboratory diagnosis of activated protein c resistance and its evaluation in a population of pregnant women(1997-10) Munster, MarionVenous thromboembolic disease is a common health problem. It contributes considerably to morbidity as well as to mortality. Thrombosis usually occurs due to an underlying risk factor which may be environmental or genetic in origin. The recently described activated Protein C (APC) resistance is the commonest cause of familial thrombophilia documented to date. The molecular lesion is a single point mutation in the factor V (FV) gene which abolishes a cleavage site whereby it is normally inactivated by APC. This defect, termed the FV Leiden mutation, is highly prevalent in normal Caucasian populations. Although it would appear to have arisen due to a founder effect, there is a paucity of data concerning non-Caucasian populations.Item Expectations of pregnant women prior to fetal ultrasound(2017) Bok, Eularnia JanineBackground Expectations and knowledge of pregnant women prior to fetal ultrasound are well documented in developed countries. Women have generally been shown to have appropriate and reasonable expectations and knowledge. The main objective of this study was to examine whether the views of women in our setting are similar to findings from studies in developed countries. Methods This was a descriptive study done on pregnant women attending the ultrasound department and antenatal clinic at Rahima Moosa Mother and Child Hospital. An interview questionnaire was administered before the ultrasound scan. Results Two hundred and fifty women were recruited. The most frequently expressed expectation was to determine sex of baby (n=154). This was followed by wanting to know the baby’s wellbeing and health (n=136). All the women interviewed had expectations. The majority of women did not know that fetal anomalies could be detected at fetal ultrasound (n=235), this was statistically significant (p=0.003) and was correlated to educational level. Almost half the women did not know the purpose of the ultrasound for which they were referred for (n=124). Conclusion Most women had appropriate expectations in keeping with studies from developed countries. Lack of education was directly linked to poor knowledge of fetal ultrasound. This study has identified areas where patient education is needed regarding fetal ultrasounds.Item The prevalence of helminth and malaria infections and the effects of de-worming on disease progression markers in HIV-1 infected pregnant women on antiretroviral therapy in Rwanda(2017) Emil, IvanBackground: Helminth and malaria co-infections have been hypothesized to be factors driving the HIV-1 epidemic in Africa, and the fact that both cause anaemia highlights the importance of addressing the interactions between HIV/AIDS, malaria and intestinal helminthic infections in pregnancy for individuals in resource limited settings. Aims: The aims of this thesis were to determine the prevalence and risk factors for malariahelminthic dual infections among HIV positive pregnant women on antiretroviral therapy in Rwanda. The second aim was to determine the effect of deworming on immune markers of HIV/AIDs disease progression among HIV-infected pregnant women on antiretroviral therapy (ART), and to elucidate the benefits of deworming, specifically in targeted versus untargeted deworming. Methods: A cross-sectional study was carried out in 328 HIV-positive pregnant women receiving ART. We determined the prevalence of helminth and malaria dual infections and the effects of ART on these infections were also examined. This cross sectional study acted as a pilot study for a deworming intervention, which took the form of a longitudinal study of targeted and untargeted deworming in which 980 HIV-infected pregnant women were randomized to ‘targeted’ and ‘untargeted’ arms with albendazole therapy. The effects of deworming on the prevalence of helminth infection and CD4 counts, viral load and haemoglobin levels were measured over time at 4 visits. Measurements were at baseline and every 3 months thereafter. The presence of Plasmodium falciparum was tested at each visit and anti-malarial therapy (Coartem: artemether-lumefantrine) was administered to all subjects who tested positive for P. falciparum. Baseline data was used to determine the risk factors for helminth infection. Helminthic infection was diagnosed using the Kato Katz method, whilst the presence of P. falciparum was identified from blood smears. The CD4 counts and viral load levels were also determined using standard laboratory methods. Results: Within the pilot study of 328 women residing in rural (n=166) and peri-urban (n=162) locations, 38% of those tested harboured helminths, 21% had malaria and 10% were infected with both. The most prevalent helminth species were Ascaris lumbricoides (20.7%), followed by Trichiuris trichiura (9.2%), Ancylostoma duodenale and Necator Americanus (1.2%). Helminth infections were characterized by low haemoglobin levels and low CD4 E. Ivan PhD thesis Page iii counts. Subjects treated with a d4T-3TC-NVP regimen had a reduced risk of Trichuris trichiura infection (OR, 0.27; 95% CIs, 0.10-0.76; p<0.05) and malaria-helminth dual infection (OR, 0.29; 95% CI, 0.11-0.75; p<0.05) compared to those receiving AZT-3TC-NVP therapy. Within the longitudinal study of deworming in 980 pregnant, HIV-infected females, analysis of the baseline data showed that education and employment reduced the risk of all types of infection whilst hand washing protected against helminth infection (0.29 [0.19-0.46]; p<0.0005). Logistic regression analysis, at baseline (odds ratio [95% CIs]), demonstrated that TDF-3TC-NVP (3.47 [2.21-5.45]; p<0.0005), D4T-3TC-NVP (2.47 [1.27-4.80]; p<0.05) and AZT-NVP (2.60 [1.33-5.08]; p<0.05) regimens each yielded higher helminth infection rates than the AZT-3TC-NVP regimen. Anti-retroviral therapy had no effect on the risk of malaria. The prevalence of P. falciparum infection was similar at all-time points for the targeted and non-targeted anti-helminth treatment arms, with a significant fall in helminth prevalence in both arms by visit 2. Albendazole therapy was associated with favourable changes in haemoglobin levels, CD4 counts and viral loads, in those subjects with helminth infections. Haemoglobin levels were similar in both arms at all study visits, rising significantly from visit 1 to visit 2 in both groups and peaking by visit 3. Thereafter, levels fell significantly (p<0.0005 for both comparisons) by visit 4. Conclusions: The prevalence of helminth infection in HIV infected pregnant women on antiretroviral therapy is common in rural and peri-urban settings in Rwanda. This study clearly shows that, albendazole treatment is associated with an increase in CD4 counts, a fall in viral loads and an increase in haemoglobin levels. The effects of albendazole are mediated by the eradication of helminth infection. The study also shows that treatment with albendazole using a targeted or non-targeted regimen is equally effective. The mechanism by which certain ART regimens reduce the risk of helminth infection warrants further study.Item Cell-Mediated and humoral immune responses to trivalent inactivated influenza vaccine in high-risk groups(2017) Malherbe, Alexander RobertIntroduction: Pregnancy is associated with physiological and immunological changes that leave women vulnerable to influenza infection and associated complications. This evolutionary adaptation is not fully understood, but evidence indicates a shift from cell-mediated immunity toward humoral immunity, which places pregnant women at a heightened risk to severe influenza illness, exacerbated further by co-infection with HIV. Tuberculosis (TB) is a major health issue resulting in ill-health among millions of people every year, with approximately one third of the population having latent TB. The considerable gains achieved in reducing the incidence of TB have reversed in recent years due to the emergence of HIV. Currently little data exist on the effectiveness of influenza vaccination in individuals co-infected with HIV and TB. We evaluate and compare the cellular and humoral immune responses to the trivalent inactivated influenza vaccine in these high-risk groups. Methods: In 2013 we conducted (1) a double-blind randomised controlled trial, involving HIV-infected pregnant women, (2) two prospective, open labelled trials involving HIV-infected non-pregnant women, and HIV-uninfected pregnant and non-pregnant women, respectively, as well as in 2014 (3) a prospective, open labelled four arm trial involving HIV/TB co-infected, HIV-infected TB-uninfected, HIV-uninfected TB-infected and HIV-uninfected TB-uninfected adults. Cell-mediated, as measured by interferon-gamma (IFN-γ) enzyme-linked immunospot (ELISPOT) assay, and humoral, as measured by hemagglutination inhibition (HAI) assay, immune responses to the seasonal iii trivalent inactivated influenza vaccine were evaluated and compared between respective study groups at baseline and approximately 1 month post-vaccination. Results: in this study we report no significant differences in cell-mediated immune (CMI) responses among HIV-infected pregnant and non-pregnant women at both pre-vaccination and post-vaccination. Vaccination improved CMI responses to all three influenza strains, with the only significant increases observed for A/H1N1 in HIV-infected pregnant and non-pregnant women and B/Yamagata in HIV-infected non-pregnant women. Following stratification of women into low- (LB) and high-baseline (HB) responses we found significantly improved cellular immune responses to the influenza viruses in the LB groups for both HIV-infected and HIV-uninfected pregnant and non-pregnant women, whereas HB women tended to exhibit a declined immune response. We show significantly enhanced humoral immune responses to the influenza vaccination in TB-infected and TB-uninfected adults living with HIV post-vaccination, with little significant differences between the two groups. We found a similar trend in HIV-uninfected adults infected with and without TB; however HIV-uninfected adults achieved higher geometric mean titers than adults living with HIV. Conclusion: among the HIV-infected pregnant and non-pregnant women, it appears pregnancy did not play as significant a role in attenuating CMI responses to vaccination as HIV infection. However, a significantly higher percentage of HIV-infected pregnant women were on antiretroviral therapy (ART) at the time of enrolment which may have influenced the role of CD4+ T-cell count on CMI responses and could possibly explain the iv similar responses observed in these two study groups. Cellular immune responses to vaccination were significantly greater in HIV-uninfected non-pregnant women compared to HIV-uninfected pregnant women, adding further evidence to the detrimental impact pregnancy has on CMI responses. Pre-existing immunity to influenza vaccination plays a major role on CMI responses following vaccination. Women with high-baseline responses tended to display decreased responses whereas women with low-baseline responses showed significantly improved responses. We propose that a potential threshold may exist where the quantity of memory T-cells reaches maximal levels in the blood system. We also show that vaccination with trivalent inactivated influenza vaccine (IIV3) was relatively immunogenic in HIV-infected TB-infected/uninfected adults, albeit not the magnitude observed in healthy populations. However, in adults living without HIV-infection, we showed that influenza vaccination was significantly immunogenic in both adults infected with TB and those without. Additionally, we show that infection with TB does not appear to affect humoral immune responses, even in the HIV-infected population.Item Natural induced antibodies against group B streptococcus surface proteins and capsular polysaccharides(2017) Dzanibe, SonwabileBackground Vaccination of pregnant women with conserved group B Streptococcus (GBS) surface proteins has the potential to confer serotype independent protection against invasive GBS disease. Susceptibility to early onset (<7 days of age) GBS disease in infants is associated with maternal recto-vaginal colonisation, low circulating maternal antibodies and reduced trans-placental transfer of antibodies specific to GBS capsular polysaccharides (CPS). Additionally, invasive GBS disease beyond infancy has been reported in individuals with underlying conditions associated with immunosuppression including HIV infection. In this study we undertook retrospective analysis of serum IgG titres against select GBS surface proteins in relation to invasive GBS disease risk factors. Methods Multiplex Luminex immunoassay was used to measure serum IgG titres against GBS capsular polysaccharides of serotype Ia, Ib, III and V and surface proteins Fibrinogen binding surface Antigen (FbsA), GBS Immunogenic Bacterial Adhesin (BibA), Surface immunogenic protein (Sip), gbs0393, gbs1356, gbs1539, gbs0392; and lipoproteins gbs0233, gbs2106 and Foldase PsrA. Furthermore, in vitro expression of Sip, gbs2106, gbs0393 and gbs1356 proteins on the surface of clinical GBS isolates was assessed by flow cytometry using protein specific polyclonal antibodies generated in rabbits. Results Retrospective analyses of serum antibody titres against GBS surface proteins and CPS were measured in children between 4-7 years of age who were either HIVinfected (n=68) or HIV-uninfected (n=77). Lower geometric meant titres (GMT, U/mL) against Sip and gbs2106 were detected in HIV-infected children (77.03 and 53.10) compared to HIV-uninfected children (196.41 and 139.11, p<0.001) respectively. Similar results were observed for antibodies against CPS, with HIV-infected children having lower IgG GMC for serotype Ib (p=0.012) and V (p=0.005). Protein specific antibody titres were measured in pregnant women at 20-25 and ≥37 weeks of gestation age who were either non-colonised or colonised with GBS in the rectal and/or vaginal tract. Acquisition of GBS colonisation in the vagina was associated with higher antibody titres compared to colonisation in the rectum for proteins Sip (p=0.049), Foldase (p=0.0094), gbs0233 (p=0.0039), gbs0393 (p=0.027), gbs1539 (p=0.0004) and gbs1356 (p=0.039). The likelihood of acquiring GBS colonisation during pregnancy was lower in women having median IgG titres against gbs0233 ≥200 U/mL (adjusted OR=0.47 [95% CI: 0.25-0.89], p=0.021) and gbs1539 ≥85 U/mL (adjusted OR=0.44 [95% CI: 0.24-0.82], p=0.01). The influence of maternal HIV infection on trans-placental transfer of antibodies against GBS surface proteins was evaluated by comparing IgG titres between 83 HIV-infected and 81 HIV-uninfected mother-newborn dyads. Maternal HIV infection was associated with reduced trans-placental transfer of antibodies, demonstrated by the difference in cord-maternal antibody ratios between HIV-infected and HIV-uninfected mothernewborn pairs for Sip (25.8%, p<0.001), Foldase (30.4%, p<0.001), gba0392 (36.5%, p=0.006), gbs0393 (32.9%, p<0.001), gbs1539 (39.2%, p<0.008), gbs2106 (35.7%, p<0.001) and BibA (19.4%, p=0.004). A case control study was used to evaluate the association of protein specific IgG titres and invasive disease in neonates and young infants born to GBS colonised mothers, including 116 with healthy infants and 66 with invasive GBS disease at <90 days of age. Lower IgG GMT were detected in neonates who developed early-onset disease compared to control infants for Sip (65.48 vs 145.43, p<0.001), Foldase (50.45 vs 109.87, p=0.005), gbs0393 (106.42 vs 221.81, p=0.006) and gbs1356 (45.34 vs 94.52, p=0.01). Similarly, young infants with late-onset disease had significantly lower IgG GMT (U/mL) compared to healthy controls for Sip (43.72 vs 79.69, p=0.04) and gbs2106 (30.46 vs 65.35, p=0.003). Infants born to women with Sip specific antibody titres ≥150 U/mL antibodies titres against Sip were 66% less likely to develop invasive disease. Of the 82 GBS isolates collected from mothers who deliverd term babies (39 with invasive GBS disease and 43 healthy controls) that were assessed for in vitro expression of specific proteins, Sip, gbs2106 and gbs0393 were expressed in 70.7% 93.9% and 87.8% GBS isolates respectively. The expression of gbs2106 on the surface of GBS was more frequent in strains of women with infants who developed invasive disease compared to those with healthy infants (100% vs 88.4%, p=0.028). The distribution of Sip and gbs0393 expression between GBS isolates from women of infants with invasive GBS disease and healthy controls was similar, 71.8% vs 69.8% (p=0.84) and 89.7% vs 86.0% (p=0.61) respectively. Among women carrying GBS strains expressing gbs2106, having antibody titres ≥100 U/mL was associated with 90% lower likelihood for delivering infants that develop invasive GBS disease (OR=0.11 [95% CI: 0.02-0.54], p=0.002). Conclusion Vulnerability to invasive GBS disease in HIV-infected immunocompromised individuals is possibly due to reduced antibody levels against CPS, Sip and gbs2106. Also, susceptibility to invasive GBS disease in infants may be exacerbated by maternal HIV-infection, which was associated with reduced transplacental transfer of antibody against GBS surface proteins. Higher maternal antibodies titres against Sip and gbs2106 proteins were associated with reduced odds of their infants developing invasive GBS disease. These data support consideration of Sip and gbs2106 proteins as possible vaccine candidates in pregnant women to protect their infants against invasive GBS disease. Furthermore, reduced GBS colonisation during pregnancy can be achieved by maternal immunisation of gbs0233 and gbs1539, which may subsequently result in lower rates of GBS transmission to newborns and thereby decreasing their risk for invasive GBS disease.Item Second trimester termination of pregnancy at Chris Hani Baragwanath academic hospital(2015-04-07) Baloyi, StephenObjectives: The main objective of this study was to characterise women who presented at Chris Hani Baragwanath Academic Hospital (CHBAH) between 12 and 20 weeks for termination of pregnancy (TOP). Secondary objectives were to determine time to abortion, compare sonar gestational age to gestational age by dates and reasons for late presentation. Method: This was a prospective cohort study of women over the age of 18 who were referred to CHBAH for second trimester TOP between August 2012 and May 2013. The exclusion criteria were pregnancies more advanced than 20 weeks gestation. Data was collected from the medical file and by interview. Demographics and reasons to terminate were extracted from the files. Outcome variables included bleeding, pain, and time to abortion. Results: One hundred and ninety one women (91.39%) aborted. The median age of women was 25.00 (IQR=21.00-31.00), range (18-43). Women older than 25 years were 33% less likely to abort than women less than 25 years of age. Ninety nine women (47.14%) bled severely. One woman had a uterine perforation following evacuation of the uterus. The median gestational age by sonar was14.71 (IQR=13.86-16.14), range (13.00-20.00). The median gestational age by dates was13.57 (IQR=12.29-15.00), range (4.14-26.28). One hundred and thirty five women (63.98%) had an MVA for RPOC using analgesia following medical induction. Two women (0.95%) needed hysterotomy following failed TOP. The median time to abortion was 11.50(IQR=8.67-17.92), range (3.50-69.33) and incidence rate of 0.5 per hour or 1 per 2hours. Conclusion: The majority of women (91%) aborted within 72 hours following medical induction with less complication rate and short induction to abortion time. This affirm misoprostol efficacy as the suitable drug for conducting second trimester medical TOP.Item Appropriateness and pregnancy outcomes of pregnant women referred to Chris Hani Baragwanath academic hospital for prolonged pregnancy(2016) Masuku, BandileBackground A pregnant woman is considered to have a prolonged pregnancy when her pregnancy has extended beyond 42 gestational weeks. The diagnosis of prolonged pregnancy is difficult to make especially when these women are not sure of their last menstrual period or never had early pregnancy ultrasounds scan. Objectives The aim of this study was to determine the appropriateness of referral and the pregnancy outcomes of women referred to CHBAH for prolonged pregnancy. Methods This was a secondary analysis of data from a cross sectional study on “predictive ability of clinical palpation for estimating amniotic fluid volume in suspected prolonged pregnancy”, considering the gestational age at the time of referral. Results One hundred women were recruited. Fifty-five of them were found to be inappropriately referred while 45 were found to be appropriately referred with no statistical difference between the two groups. Conclusion The majority of the referrals were inappropriate.