In 2013, 2 million people were newly infected with HIV, and 11% of those new infections were infants that obtained the disease from their mother. In resource poor settings, like Sub-Saharan Africa, infection rates from mother to child can range from 15-45%. With proper prevention of mother to child transmission (MTCT), these rates can drop to 5%. Proper prevention includes the use of antiretroviral treatment (ART) during pregnancy, delivery, and post-partum and breastfeeding. In 2010, WHO proposed a model that required all HIV positive mothers to receive ART. The model successfully increased the amount of women on treatment, and many countries also saw a decrease in the rate of MTCT, however barriers still exist. In my thesis, I explain how HIV attacks an individual’s immune system, and why it has been such a difficult epidemic to control in regards to mother to child transmission. I also examine how different models of prevention are successful, and why Option B+, proposed by WHO in 2010, has been the most successful. Lastly, I propose new additions to the model in an attempt to circumvent the barriers.

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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

Philosophiae Doctor - PhD / The HIV/AIDS epidemic remains an unbeaten challenge that affects all parts of the global population. Since the identification of the epidemic in the early 1980s, nearly 58 million people have become infected with the virus and 25 million people have died of HIV-related complications. This study aimed to elucidate individual and community level factors associated with the uptake of antenatal care (ANC), health facility delivery, HIV Counselling and Testing (HCT), and Prevention of Mother-to-Child Transmission of HIV (PMTCT) services by implementing a hierarchical (multilevel) methodological approach. This study used a cross-sectional, multistage sampling design in which health facilities were first selected (stage 1), followed by recruitment of post-partum women who came for child immunization from each health facility (stage 2), in Tigray region. Structured interview guides were developed for interviews. Four-fifths (80.0%) of mothers used antenatal services at least once during their most recent pregnancy and of these 74.6% of women accessed HCT. Sixty nine percent of women had delivered at a health facility, 79% of mothers and 55.7% of their children had received PMTCT services. Place of residence was significantly associated with ANC attendance and place of delivery, with women living in urban areas almost 2 times (OR=1.75, 95% CI 1.06, 2.92) more likely to deliver at a health facility. With the addition of one health facility per 25000 people, the likelihood of delivering at a health facility increased by 2.45 fold (OR=2.45, 95% CI 1.04, 5.78). Attending ANC (OR=4.54; 95%CI 2.82,7.33) and getting support from husband (OR=1.97; 95%CI 1.25,3.10) were significantly associated with HCT, at the individual level. At the community-level, for the addition iii of one health facility and HCT site for every 25000 people increase the likelihood of HCT utilization by 2.1 and 2.4 fold respectively. Mothers who delivered at a health facility were 18 times (OR=18.21; 95%CI 4.37,75.91) and children born at a health facility were 5 times (OR=4.77; 95%CI 1.21,18.83) more likely to receive PMTCT services, compared to mothers delivering at home. With the addition of one nurse per 1500 people, the likelihood of getting PMTCT services for a mother increases by 7.22 fold (OR=7.22; 95% CI 1.02,51.26). Community-level random-effects were also significant and there was confirmation of nesting at the community-level even after controlling for individual and communitylevel variables. Findings also showed that HCT utilization was nested according to district of residence, contributing 11.3% of the variance. In addition, the variation of mothers getting PMTCT services between districts was only 0.6%, but was 27.2% for children. Conclusion: Factors influencing utilization of maternal health services work at different levels, individual and community. Hierarchical models reveal these differences in ways that single-level (individual or community) models do not. Interventions are needed to increase spouse involvement in ANC utilization, and explore effective ways of increasing health facility delivery among poor women with little formal education in rural areas and increasing the number of health facility per people are important. The government should focus on increasing ANC access, educating couples on the importance of health services utilization, increasing the number of health facilities and HCT sites per population to improve HCT utilization. In addition to these, programmes should focus on increasing health facility delivery, training traditional birth attendants to understand the need for PMTCT and increasing iv HCT coverage to advance getting PMTCT services for mothers at the individual level and for children at both individual and community level. Permission to conduct the study was granted from the Ethics Committee of the University of the Western Cape and from Tigray Region Health Bureau. Verbal informed consent was obtained from each participant in the health facility based interview.