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Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2013-10-18T17:18:19Z No. of bitstreams: 1 Tamiris Tatiane Dias Analise de quasespecies...2013.pdf: 8521760 bytes, checksum: 4e4fc2d3b2f4ee514d97744b378b3fe0 (MD5) / Made available in DSpace on 2013-10-18T17:18:19Z (GMT). No. of bitstreams: 1 Tamiris Tatiane Dias Analise de quasespecies...2013.pdf: 8521760 bytes, checksum: 4e4fc2d3b2f4ee514d97744b378b3fe0 (MD5) Previous issue date: 2013 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / A transmissão materno-infantil (TMI) é a causa mais comum de infecção pelo vírus da hepatite C (HCV) entre as crianças. Objetivo: Esse estudo teve como objetivo avaliar fatores virais implicados na TMI do HCV. Materiais e métodos: Quatro gestantes e um par mãe-recém-nascido (RN), todos infectados pelo HCV, foram incluídos neste estudo. Sequências das regiões 5’UTR, E1, HVR1, E2 e NS5B foram obtidas através de sequenciamento direto do produto do PCR e clonagem. A diversidade quasiespécie foi analisada utilizando-se diferentes parâmetros (taxa de clonotipos, frequência de mutações, Pn e entropia de Shannon normalizada), comparando (1) grupos TMI+ e TMI-, e (2) par mãe-RN. Um framework foi usado para avaliar a associação entre a frequência dos nucleotídeos e a TMI. Resultados: Dois casos de TMI foram identificados, mas apenas a amostra de um RN estava disponível. As cargas virais de todos os sujeitos estavam acima do limite de quantificação. Ambos os casos de TMI pertenciam ao genótipo 1a apenas este subtipo foi analisado subsequentemente. O sequenciamento direto dos produtos de PCR não representou, de maneira confiável, a complexidade quasiespécie e não foi utilizado. Não houve clonotipos coincidentes entre os grupos TMI+ e TMI-, exceto pela região 5’UTR. Em nível de aminoácido, mãe e RN compartilharam apenas do clonotipo predominante. Todos os clonotipos minoritários foram exclusivos. Foi observada maior diversidade quasiespécie nas regiões E2 e NS5B. A HVR1 apresentou a menor diversidade dentro da região codificante. A diversidade quasiespécie do grupo TMI+ foi sempre maior do que aquela vista no grupo TMI-; no entanto, não houve significância estatística. Trinta e cinco mutações na região codificante foram associadas significativamente com a TMI. Dados do par mãe-RN sugerem que a transmissão intrauterina ocorreu em um momento inicial da gestação e que o vírus provavelmente atravessou o tecido placentário, levando a um gargalo de garrafa. Conclusões: A diversidade quasiespécie não foi associada à TMI, mas a presença de mutações ao longo da região codificante sugere que o genoma completo contribui para a capacidade de transmissão intrauterina. São necessários estudos adicionais para determinar se essas variantes podem ser úteis para predizer a TMI. / Introduction: Mother-to-child-transmission (MTCT) is the most common cause of hepatitis C virus (HCV) infection in children. Objective: This study aimed to evaluate viral factors implicated in HCV MTCT. Methods: Four HCV-infected pregnant women and one HCV-infected mother-newborn pair were included in this study. Sequences were obtained from the regions 5’UTR, E1, HVR1, E2 and NS5B by direct PCR product sequencing and cloning. Quasispecies diversity was analyzed by different parameters (clonotype ratio, mutation frequency, Pn and normalized Shannon entropy), comparing (1) MTCT+ vs. MTCT- groups, and (2) mother-newborn pair. A framework was used to establish association between nucleotide frequency and MTCT. Results: Two cases of MTCT were identified, but a sample from only one newborn was available. Viral loads from all subjects were above the quantification limit. Both cases of MTCT belonged to genotype 1a and only this subtype was further analyzed. Direct sequencing from PCR products did not reliably represent the quasispecies complexity and was not used. There were no coincident clonotypes between MTCT+ and MTCT- groups, except for 5’UTR. At the amino acid level, mother and newborn shared only the master clonotype. All minor clonotypes were exclusive. Higher quasispecies diversity was observed within E2 and NS5B regions. HVR1 presented the lowest diversity within the coding region. Quasispecies diversity from the MTCT+ group was always greater than seen in the MTCT- group; however, no statistically significance was observed. Thirty-five mutations in the coding regions were significantly associated with MTCT. Data from the mother-newborn pair suggest that the intrauterine transmission occurred in an earlier time point of the pregnancy and that the virus probably crossed the placental tissue leading to a bottleneck. Conclusions: Quasispecies diversity was not associated with MTCT but the presence of mutations along the coding region suggests that the whole genome contributes to the ability of intrauterine transmission. Further studies are required to establish if these variants could be useful to predict MTCT.

The study sought to determine the meaning and interpretation by facility managers and nurses on utilisation of expanded programme on immunisation and integrated management of childhood illnesses (EPI and IMCI) programmes for follow-up and antibody testing of HIV-exposed infants (HEI) at 18 months. Also to understand the factors within the health systems that influence the follow-up and antibody testing. The study setting selected was six facilities in Steve Tshwete subdistrict in Nkangala district of Mpumalanga province in South Africa. The study used a hermeneutic phenomenology using in-depth interviews for collecting data from 4 facility managers and 12 nurses. The major themes that emerged from the interviews were referral, defaulting, integration, stigma, and off-site ART initiation within the health system. These were found to influence the utilisation of HEI and IMCI services for follow-up and management of HEI. It was also found that the importance of integrating the management of HEI into the EPI and IMCI cannot be overemphasised. It was concluded that the Health Department needs to be vigilant and use all available resources to manage HEI to meet the MDG 4 of prevention of infant mortality / Health Studies / M.A. (Nursing Science)

The prevalence of female adults and adolescents living with diagnosed HIV infection continues to rise. Latina women in the United States (US) are not only disproportionately affected by human immunodeficiency virus (HIV) infection, but also underutilize HIV prevention services, such as HIV testing. Data are limited on the differences in HIV risk among Latinas by country of birth, and opportunities still exist to prevent transmission of HIV and reduce HIV-related disparities. This dissertation describes the risk behaviors, testing behaviors, and test results among women tested for HIV at public sites in Florida. Additionally, it compares these characteristics by HIV testing site type among pregnant women. Multivariable logistic regression was used to estimate the adjusted odds ratios (AOR) and associated 95% confidence intervals for the outcome variables of risk behaviors, previous testing, and positive HIV test results. Of the total 209,954 records, 184,037 were from women not currently pregnant, of which 87,569 (45.6%) were among non-Hispanic Blacks (NHBs), 47,926 (26.0%) non-Hispanic Whites (NHWs), and 41,117 (22.3%) Latinas. Women who reported previous HIV testing had decreased odds of being Latina compared to NHW women (AOR 0.90; 95% confidence interval [CI] 0.87, 0.94), and testing event results indicate that foreign-born Latina women were significantly less likely to report partner risk (AOR 0.42; 95% CI: 0.40-0.54) than US-born Latina women. Of the 24,863 records of pregnant women, 10,199 (41.1%) were among Latinas, 6,796 (27.4%) were among NHB, and 6,631 (26.7%) were among NHW. The testing records indicated that Latina and NHB women had decreased odds of reporting partner risk than NHW women (Latina: AOR 0.20; 95% CI: 0.14-0.28; and NHB: AOR 0.14; 95% CI: 0.10-0.21), and records of women tested in prisons/jails had higher odds of reporting previous HIV testing compared to prenatal care sites (AOR 1.86; 95% CI: 1.03-3.39). Reported risk behaviors varied by race/ethnicity and Latina country of origin. Knowledge of these differences can enhance current testing and prevention strategies for women, and aid in targeting HIV prevention messaging, program decision-making, and allocation of resources, corresponding to the central approach of High Impact Prevention and the National HIV/AIDS Strategy.

Magister Public Health - MPH / This study explores the challenges faced by nurse counselors in the implementation of HIV and Infant Feeding Policy in Amathole District of the Eastern Cape. Objectives: (i) To describe the demographic characteristics of the study population; (ii) To explore the challenges faced by nurse counselors in the implementation of current HIV and infant feeding policy and guidelines; (iii) To establish the nurse counselors perspectives on the infant feeding policy and guidelines for HIV positive mothers; (iv) To examine the support system available to the nurse counselors who give infant feeding advice to HIV positive mothers. / South Africa

Magister Public Health - MPH / Aim: To establish whether a family centered approach to HIV care in which HIV positive adults are counseled on the importance of having their children tested results in the adults bringing their children under the age of five years for testing and or accessing HIV care, and to explore challenges faced by caregivers in bringing children for testing and care. / South Africa

Magister Scientiae (Biodiversity and Conservation Biology) - MSc (Biodiv and Cons Biol) / W.H.O infant feeding options are presented as a package in the prevention of HIV transmission from mother to child. These infant feeding options are namely exclusive breastfeeding, replacement feeding and other options such as wet nursing by a tested HIV negative woman and heat treated breast milk. However, in Zambia, like many other poor countries, the cultural attitude towards breastfeeding is that the breastfeeding period generally goes up to two years. This traditional way of feeding is so much rooted in local culture that any cessation of breastfeeding or any introduction of alternative feeding would be a source of concern at community and family levels. In addition, it is a well known fact that stigma and discrimination are still high in the country. It is with this background that we decided to carry out a study in Mongu district which aimed at assessing HIV positive mothers’ knowledge of WHO infant feeding options and looking at the challenges they face vis-à-vis these recommended feeding options. DATA COLLECTION METHODS A total of 10 experienced nurses, who have been working in the HIV/AIDS programme for more than 15 years, were trained in data collection. During home visit, semistructured questionnaires were used during face- to- face interviews of each HIV positive mother who voluntarily took part in the study. SAMPLING AND SAMPLE SIZE Systematic sampling technique was used to constitute our study sample. With this technique, a complete list of 5317 HIV positive mothers was constituted by listing all HIV positive mothers whose names were in the registers of PMTCT at the selected health institutions, and who had infants whose ages ranged from 6 months to 2 years. 1636 HIV positive mothers had babies whose ages were ranging between 6 months and 2 years. Out of the 1636 we selected randomly the first participant from the complete list, and then we went on selecting every 8th HIV positive mother up to the time we constituted a sample of 200 participants. Thereafter, the selected HIV positive mothers were visited individually in their respective households for interview by trained interviewers. During home visit, 5 selected participants declined to take part in our study while 195 HIV mothers voluntarily accepted to be interviewed. RESULTS Analysis of data collected from 195 HIV positive mothers revealed that 144 study participants or 73.8 %( 95% C I 67.6-80%) of all participants knew their status through the PMTCT programme where the “opt out” approach was used to routinely screen pregnant women for HIV during ante natal visit or when admitted to labour wards. It was also established that the assessment of knowledge among study participants of exclusive breastfeeding period was good. 96.9 %( 95% CI 95.66-98.14%) of participants stated that 6 months was the recommended duration for exclusive breastfeeding when the mother is HIV positive while only 3.07 %( 95% CI 0.65-5.49%) said that exclusive breastfeeding should go beyond 6 months. It was discovered that the majority of HIV positive mothers or 166 participants representing 85.1%(95% CI 80.1-90.1%) who participated in our study considered mixed- feeding as not appropriate for infant born from HIV positive mothers while 29 participants or 14.8%(95% CI 9.8-19.8%) said that mixed feeding was recommendable. It was also found that 95 participants representing 48.7 %( 95% CI 41.6- 55.7%) opted for exclusive breastfeeding, 61 participants or 31.2% (95% CI 24.7-37.7%) participants opted for formula milk while 39 or 20 %( 95% CI 14.4- 25.6%) of participants were mixed-feeding. It was discovered that 118 participants had breastfed. Among them, 53.4 %( 95% CI 46.4-60.4%) participants said that they had breastfeed for up to 6 months while 46.6 %( 95% CI 43-50.2%) said they had breastfeed for more than 6 months. Among those who had breastfed for more than 6 months, 58.1 %( 95% CI 54.6-61.6%) said that they had done so because of financial constraints; 21.8 %( 95% CI 16-27.6%) for fear of discrimination and stigmatization; and 20 %( 95% CI 14.4-25.6%) for fear of discrimination and stigmatization and financial constraints. We also discovered during our research that for the majority of study participants or 81.5%, the decision to opt for one of the infant feeding options was a product of discussion between the HIV positive mothers and other persons such as the husband, friends, relatives and health care provider. CONCLUSION In our study we discovered that though the knowledge of PMTCT and WHO infant feeding options among study participants was good, fear of stigmatization, discrimination and abandonment was high among interviewees. This fear explains why the implementation of WHO infant feeding options is still a serious challenge amongst HIV positive mothers in Mongu, as many HIV positive mothers do not want to be seen in the community as people carrying the virus. It is also for the same reason that our study participants had to choose people to whom to talk to about their HIV positive status and with who to discuss their chosen infant feeding options. Further, due to the high level of poverty among Mongu residents, financial constraint was another major challenge in the implementation of WHO recommended infants feeding options.

Magister Public Health - MPH / Background: Globally, neonatal mortality (i.e. deaths occurring during the first month of life) accounts for 44% of the 11 million infants that die every year (Lawn, Cousens Zupan, 2005). Early detection of illness and referral of mothers and infants during the peri-natal period to higher levels of care can lead to substantial reductions in maternal and child mortality in developing countries. Establishing effective referral systems from the community to health facilities can be achieved through greater utilization of community health workers and improved health seeking behaviour. Study design: The Good Start Saving Newborn Lives study being conducted in Umlazi, KwaZulu-Natal, is a community randomized trial to assess the effect of an integrated home visit package delivered to mothers during pregnancy and post delivery on uptake of PMTCT interventions and appropriate newborn care practices. The home visit package is delivered by community health workers in fifteen intervention clusters. Control clusters receive routine health facility antenatal and postpartum care. For any identified danger signs during a home visit, community health workers write a referral and if necessary refer infants to a local clinic or hospital. The aim of this study was to assess the effectiveness of this referral system by describing community health worker referral completion rates as well as health-care seeking practices and perceptions of mothers. A cross- sectional survey was undertaken using a structured questionnaire with all mothers who had been referred to a clinic or hospital by a community health worker since the start of the Good Start Saving Newborn Lives Trial. Data collection: Informed consent was obtained from willing participants. Interviews were conducted by a trained research assistant in the mothers home or at the study offices. Road to Health Cards were reviewed to confirm referral completion. Data was collected by means of a cell phone (mobile researcher software) and the database was later transferred to Epi-info and STATA IC 11 for analysis. Descriptive analysis was conducted so as to establish associations between explanatory factors and referral completion and to describe referral processes experienced by caregivers. Significant associations between categorical variables were assessed using chi square tests and continuous variables using analysis of variance. Results: A total of 2423 women were enrolled in the SNL study and 148 had received a referral for a sick infant by a CHW by June 2010. The majority (95%) of infants were referred only once during the time of enrolment, the highest number of which occurred within the first 4 weeks of life (62%) with 22% of these being between birth and 2 weeks of age. Almost all mothers (95%) completed the referral by taking their child to a health facility. Difficulty in breathing and rash accounted for the highest number of referrals (26% and 19% respectively). None of the six mothers who did not complete referral recognised any danger signs in their infants. In only 16% of cases did a health worker give written feedback on the outcome of the referral to the referring CHW. Conclusion: This study found high compliance with referrals for sick infants by community health workers in Umlazi. This supports the current primary health care re-engineering process being undertaken by the South African National Department of Health (SANDOH) which will involve the establishment of family health worker teams including community health workers. A key function of these workers will be to conduct antenatal and postnatal visits to women in their homes and to identify and refer ill children. Failure of mothers to identify danger signs in the infant was associated with non-completion of referral. This highlights the need for thorough counseling of mothers during the antenatal and early postnatal period on neonatal danger signs which can be reinforced by community health workers. Most of the referrals in this study were neonates which strengthens the need for home visit packages delivered by community health workers during the antenatal and post-natal period as currently planned by the South African National Department of Health.Recommendations: This study supports the current plans of the Department of Health for greater involvement of CHWs in Primary Health Care. Attention should be given to improving communication between health facilities and CHWs to ensure continuity of care and greater realization of a team approach to PHC. / South Africa

Grâce aux combinaison d’antirétroviraux (ART), le taux de transmission mère-enfant (TME) du Virus de l’Immunodéficience Humaine VIH est maintenant réduit à moins de 1%. Des progrès restent néanmoins à faire, en particuliers chez les femmes débutant tardivement leurs consultations prénatales. Mais l’évaluation de nouvelles stratégies ART pour la prévention de la TME (PTME) devient de plus en plus complexe à cause des exigences statistiques liées au fait que les transmissions sont rares. Dés lors, il devient crucial de modéliser l’efficacité des ART sur la charge virale (CV) et la transmission. Dans cette thèse, nous modélisons les mécanismes et le moment de la TME du VIH en utilisant des modèles mixtes. Les données proviennent de 4 études de prévention périnatales du VIH en Thaïlande (PHPT-1, PHPT-2, PHPT-5 1st phase et PHPT-5 2nd phase), une base de données historiques de qualité, collectées de 1996 à 2015, où différentes prophylaxies ART ont été prescrites à plus de 4000 femmes enceintes pendant des durées variables: Zidovudine (ZDV) seule; ZDV + une dose unique de nevirapine périnatale (sdNVP); ZDV+lopinavir/ritonavir (LPV/r) ou ZDV+LPV/r+lamivudine (3TC). Les modèles développés apportent un éclairage sur les mécanismes et le moment de la PTME ainsi que sur le rôle respectif de différents ART sur la réduction de la CV et sur leur contribution à la prophylaxie pre/post exposition. Partant de ces connaissances, une approche bayésienne est appliquée à une étude de cas (essai de supériorité dans le contexte d’un événement rare comme la TME du VIH) afin d’améliorer la puissance statistique tout en limitant la taille de l’échantillon, et comparée à une approche fréquentiste. / Nowadays, with the use of highly efficacious antiretroviral (ART) combination, the rate of mother-to-child transmission (MTCT) of Human Immunodeficiency Virus (HIV) is reduced to less than 1%. However, there are still some gaps to be filled, especially in women who initiate antenatal prophylaxis late. The evaluation of new ART strategies or drug combinations for the prevention of MTCT (PMTCT) of HIV becomes more difficult in view of the statistical requirements in case of rare outcomes. Therefore modeling the impact of ART on maternal viral load (VL) and transmission rate is increasingly important. In this thesis, the mechanisms and timing of MTCT of HIV were investigated using mixed model approaches. Data were derived from four perinatal HIV prevention studies in Thailand (PHPT-1, PHPT-2, PHPT-5 1st phase and PHPT-5 2nd phase), a unique set of quality historical data, consistently collected from 1996 to 2015, in which different ART prophylaxis regimens were provided to more than 4000 HIV-infected pregnant women for varying durations: Zidovudine (ZDV) alone; ZDV plus perinatal single dose nevirapine; ZDV+lopinavir/ritonavir (LPV/r) or ZDV+LPV/r+lamivudine. The developed models provide insights on the mechanisms and timing of PMTCT as well as on the respective role of different ARTs on the maternal VL reduction and in turn on their contribution to pre/post-exposure prophylaxis in MTCT of HIV. With this prior knowledge, a Bayesian design is applied to a case study, a trial aimed at evaluating treatment superiority in the context of rare outcomes such as MTCT of HIV, to improve the statistical power –while limiting sample size— and compared to a frequentist design.

Thesis (MPH.) -- University of Limpopo, 2021 / Introduction: HIV/AIDS remains a disease of public health importance and mother-to-child transmission (MTCT) is one of the major problems. Sub-Saharan Africa is the most severely affected region, accounting for more than 90 percent of paediatric HIV infections. Most of these infections occurred during pregnancy, delivery or breastfeeding making the prevention of mother-to-child transmission (PMTCT) a public health priority. Over the last few years, efforts have been made in Sub-Saharan countries to improve PMTCT and the success of prevention of mother‐to‐child transmission of HIV (PMTCT) is dependent upon high retention of mother‐infant pairs within the PMTCT cascade. Assessing the risk factors for MTCT will help to decrease child morbidity and mortality and strengthen PMTCT programs as there is dearth of evidence regarding factors determining MTCT HIV infection to infants born to HIV positive mothers. The purpose of this study was to investigate the determinants for the human Immunodeficiency Virus positivity rates in the Greater Letaba Municipality. The study objectives were to describe the demographic characteristics of mothers and babies who tested polymerase chain reaction test (PCR)-positive in the Greater Letaba Municipality during the two-year period from 2015 to 2016, in order to determine maternal and neonatal factors associated with high positive PCR; and to determine health system-related factors associated with a high positive PCR result. Methodology The current study followed a quantitative approach in which convenient and purposive sampling was used, focusing on records of infants born from HIV-positive women in all clinics at Greater Letaba Municipality were reviewed. All records of infants who were tested for HIV and the PCR results were positive from birth up to 12 months of age were retrospectively reviewed and for the health care workers, all nurses working as managers of a clinic were interviewed. The Statistical Package for the Social Sciences (SPSS) version 23 computer software and Stata 15 was used. for comparison of categorical variables was done using a Chi-Squared test, whereas continuous variables were compared using a t-test and P-value of <0.05 was considered significant. To determine maternal and neonatal factors associated with high positive PCR, Factor analysis was used with rotated factor loadings done using the Varimax method. Results: A total of 107 records were retrieved and audited. Fisher’s exact test was used to determine the relationship between selected variables, where p<0.05 was set as level of significance. The findings reveal that the number of infants exposed to HIV during pregnancy has steadily increased. The current study further indicates that health system factors such as unskilled or untrained NIM-ART nurses in the facilities is a contributory factor to infant’s positivity rate in Greater Letaba hospital. Equal proportions of both male and female babies were found to be PCR positive at 6 weeks. The study further revealed that the highest proportion of the mothers who gave birth to PCR positive babies for the reporting period were married mothers, in the age group 25-29 years (46.1%). The second largest proportion of mothers who gave birth to PCR positive babies were single mothers in the age group 25-29 years (38.4%). The results show that high PCR positivity can be attributed to about 5 main Factors namely: maternal antenatal history (22% contribution to total variance), maternal HIV care history (18% contribution to total variance), measures of adherence to treatment (17% contribution to total variance), maternal exposure to HIV (14% contribution to total variance) and lastly the ART regimen (12% contribution to total variance). Conclusion: The study findings revealed that there is still vertical transmission of HIV to infants and the prevalence of HIV among infants born from seropositive mothers despite the availability of the latest Prevention of Mother to Child Transmission (PMTCT) Guidelines in all health care facilities. Even though transmission is reduced to the meaningful number (< 5%), there are still appropriate measures that should be taken to reduce the transmission of HIV from mothers to infants. The delayed diagnosis, adherence to ART by mothers, infant ARV prophylaxis at birth and feeding practices contributed the vertical transmission of HIV to infants. Strengthening of the PMTCT of HIV programme, increasing antenatal HIV screening and linking it to care and treatment of HIV positive mothers to obtain zero infant HIV prevalence in the region. Infant prophylaxis and maternal PMTCT interventions should be provided to all exposed infants and mothers based on the guidelines by the health institutions. Nurse-initiated management of antiretroviral treatment (NIM-ART) training of professional nurses is being offered by the Department of Health in South Africa, but it does not yield positive results as far as the PMTCT is concerned. This may be due to shortage of staff, especially trained professional nurses (PN), as well as the workload. Key concepts: Infant and Human immune deficiency virus