Dissertations / Theses on the topic 'Reproductive infections'

Reproductive tract infections (R TIs), including but not limited to the sexually transmitted infections (STIs), are currently high on the public health agendas of most low-income countries. The reasons for this are manifold, but important contributing factors include the need to control the spread ofIDV, and the high costs to health care systems and infected individuals as a consequence of un- or mis-diagnosed infections. Strategies for the control and management of these infections in resource-poor settings have been advanced at a global policy level: syndromic management of symptomatic men and women is recommended in the absence of comprehensive laboratory facilities. This thesis describes a large cross sectional survey assessing the populationbased prevalence ofRTIs in one rural area of Bangladesh. The prevalence of these infections was determined from random selections of women and men. Patterns of health-care seeking behaviour were analysed, and the correlation between reported 5,ymptoms and the presence of infection was investigated. The prevalence of syphilis in pregnant women, and the incidence of ophthalmia neonatorum were also determined, and the cost-benefit of control strategies for these two problems in this population were investigated. Given that management of symptomatic persons forms a cornerstone of most national RTIISTI control programmes, the study described in this thesis also evaluated the efficacy of the most common syndromic algorithm in use (that for treating women with vaginal discharge). Training requirements for integrating the algorithm at primary health care level are also discussed as part of the findings, and finally the cost-effectiveness of the recommended algorithm was evaluated. Using the results of the five arms of the study, recommendations are advanced for RTIISTI control programmes in areas with similar epidemiological characteristics to those found in the population described in this study. Finally, areas where further research is needed are highlighted in the discussion.

Sexually transmitted infections (STIs) continue to be a significant public health problem with an increased burden on women of reproductive age. These infections can be transmitted between humans by means of sexual activity including vaginal intercourse, oral sex and anal sex. Having a STI increases the risk of acquiring human immune-deficiency virus (HIV), hence the control of STIs is recommended for HIV prevention. The most common STI disease presentations to the public health setting in South Africa are male urethritis syndrome (MUS) and vaginal discharge syndrome (VDS). The main pathogens responsible for these two syndromes are: Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis. In the late 1990s the South African health department introduced the STI syndromic management approach into the primary health care setting. This approach aims to treat the common causes of STI syndromes through the use of specific treatment algorithms. It is cost effective because it allows treating the majority of STI patients without the need of laboratory diagnosis to determine the aetiological agent. People without any clear symptoms will remain untreated by the syndromic management approach. Little is known of the STI pathogens circulating in reproductive age women in the Tshwane region. The purpose of this study was to determine the prevalence of T. vaginalis and its co-infection in reproductive age women. This study included self-collected vaginal swabs obtained from 117 consenting reproductive age women visiting either a public health clinic or a sexual private health clinic. The swabs were cultured upon receipt in the laboratory on chocolate agar and in the InPouchTV for detection and diagnosis of N. gonorrhoeae and T. vaginalis respectively. The Nugent scoring system was used to diagnose bacterial vaginosis. The STI causing pathogens were detected on different molecular platforms which included Anyplex II STI-7 real-time PCR, GeneXpert CT/NG and GeneXpert TV. The overall prevalence for both clinics of STIs was 13.7% (16/117) and for T. vaginalis specifically, a 10.3% (12/117) rate was observed. A co-infection rate of 2.6% (3/117) was observed in this study. Trichomonas vaginalis occurred mostly with C. trachomatis (12.5%) followed by N. gonorrhoeae (6.3%). Most co-infections were observed in women of younger than 30 years old. Age was not significantly associated with the prevalent T. vaginalis infection in this study but being unmarried showed a significant association (p-value=0.038) with the prevalent infection in both clinics. The high rates of Trichomonas vaginalis and coinfections with C. trachomatis and N. gonorrhoeae observed in the asymptomatic women visiting the two clinics provide evidence that in certain key groups the simultaneous screening for all three pathogens should be performed.
Dissertation (MSc)--University of Pretoria, 2017.
Medical Microbiology
MSc
Unrestricted

Thesis (MScMedSc)--Stellenbosch University, 2012.
ENGLISH ABSTRACT: The basic semen analysis plays a pivotal role in the diagnosis of male infertility and makes a significant contribution to the diagnostic process in andrology, gynecology and clinical urology. In 1902, the man considered to be ―the founding father of modern andrology‖ Edward Martin, proposed that an analysis of a semen sample should be incorporated into all infertility assessments. Following this suggestion in 1956, the scientist John MacLeod advanced the basic semen analysis from beyond a mere observation and introduced the importance of certain semen parameters such as morphology, motility and viscosity. The present day examination includes the analysis of certain established semen parameters, which can provide key information about the quality of a patient‘s semen and the functional competence of the spermatozoa. A semen analysis is also a valuable diagnostic tool in assessing possible disorders of the male genital tract and the secretory pattern of the male accessory sex glands. This information can help to determine the reproductive capacity of the male and can be used in conjunction with the partner to indicate the impact of male genital pathophysiology in the assessment of a couple‘s prospect for fertility. Patients attending the andrology laboratory at Tygerberg Academic Hospital for a semen analysis are referred based on primary, secondary or idiopathic infertility. Amongst these patients, an increase in semen viscosity has been observed over a period of time and created the need to assess the possible causes behind this trend. Despite viscosity being included in a routine spermiogram, it raises a considerable amount of concern as it is assessed semi-quantitatively. In the first part of this study, the possible correlation between seminal hyperviscosity and leukocytospermia was assessed. To achieve the most comprehensive assessment of viscosity, a new approach was used, which is a highly quantitative method to record viscosity in the international unit, centipoise (cP). The analysis of semen samples for possible leukocytospermia was approached by three methods the first of which was cytological. During this method granulocyte grading was performed on stained semen smears during the normal determination of morphology. The same approach was taken for the second method, whereby white blood cell concentrations were quantified with a leukocyte peroxidase test in the total sample group (n=200). Viscosity was compared between the samples classified as leukocytospermic positive or negative, according to the set reference values of the World Health Organisation (WHO). Correlation analysis between the two variables was also performed. In the biochemical approach of detecting leukocytospermia, an enzyme-linked immunoabsorbant assay (ELISA) was used to quantify the concentration of the extracellular polymorphonuclear (PMN) enzyme released from leukocytes. This test was performed on 124 randomly selected samples. All samples were fractionated before storage in liquid nitrogen, to allow for multiple assessments to be performed on each sample. The PMN elastase concentration was assessed against viscosity to investigate a possible correlation and relationship with the presence of leukocytospermia. All three methods of detecting possible infection showed a significantly positive relationship with increased viscosity in semen samples. The second approach in the study was to assess increased viscosity and leukocytospermia against parameters included in the spermiogram. An evaluation of hyperviscosity and its correlations to the various other semen parameters can allow for a detailed study into the effects that this anomaly may elicit. With the assessment of each of the sperm parameters against the leukocyte count and viscosity (cP), volume, concentration and morphology showed significance. To further the study, the third angle was to investigate a possible correlation between viscosity and the functional status of the male accessory sex glands. The biochemical approach of assessing the secretory patterns of the prostate and seminal vesicles against markers of infection can possibly further the understanding behind hyperviscous semen and leukocytospermia. Citric acid and fructose, secretory products of the prostate and seminal vesicles respectively, showed no significance when assessed against the leukocyte count and viscosity. However, this project was a pilot study and this approach offers an exciting avenue for further research. These research findings may provide a more comprehensive assessment of a man‘s fertility status. Seen in the context of patients attending the andrology laboratory of Tygerberg Academic Hospital, this is greatly needed as the majority of these patients cannot afford advanced assisted reproductive therapies. The introduction of a more accurate method of quantifying viscosity may possibly help to identify, diagnose and treat patients suffering from leukocytospermia in order to ultimately enhance their fertility potential.
AFRIKAANSE OPSOMMING: Die basiese semenanalise speel 'n belangrike rol in die diagnose van manlike infertiliteit en maak dus 'n betekenisvolle bydrae tot die diagnostiese proses in andrologie, ginekologie en kliniese urologie. In 1902 het Edward Martin, wat deur sommige navorsers as die vader van moderne andrologie beskou word, voorgestel dat 'n semenanalise deel moet vorm van alle infertiliteitsondersoeke. In 1956 het die wetenskaplike John MacLeod aanvoorwerk gedoen om die grondslag van 'n basiese semenanalise daar te stel, wat beteken het dat, in plaas van net 'n observasie studie te doen, 'n semenmonster kwantitatief analiseer moes word en dat parameters soos spermmorfologie, motiliteit en viskositeit as deel van die volledige analise gedoen moet word. Die hedendaagse analise sluit, behalwe die basiese semenparameters, ook inligting in oor die funksionele aspekte van spermatozoa. Die semenanalise is dus ook ‗n belangrike diagnostiese hulpmiddel om inligting rakende moontlike abnormaliteite in die manlike genitale traktus en die sekretoriese funksies van die manlike bykomstige geslagskliere te verskaf. Hierdie inligting kan help om 'n moontlike diagnose van die man se fertiliteitspotensiaal te maak. Terselftertyd kan dit ook tesame met die metgesel se reproduktiewe inligting meer lig werp op die impak van die man se genitale patofisiologie op die paartjie se fertilitetspotensiaal. Pasiënte wat die andrologielaboratorium van die Tygerberg Akademiese Hospitaal besoek word verwys op grond van primêre, sekondêre of idopatiese infertiliteit. Gedurende die laaste aantal jare is daar ‗n toename in voorkoms van verhoogde semenviskositeit onder hierdie groep pasiënte waargeneem. Dit het die behoefte laat ontstaan om die moontlike redes hiervoor te ondersoek. Ten spyte van die feit dat viskositeit deel vorm van die roetine semenanalise is dit tog kommerwekkend aangesien dit op 'n semi-kwantitatiewe manier bepaal word. In die eerste deel van hierdie studie is 'n moontlik korrelasie tussen seminale hiperviskositeit en leukositospermie ondersoek. Om die beste moontlike verwantskap te kon bepaal is 'n nuwe en hoogs kwantitatiewe metode gebruik om viskositeit in numeriese waardes volgens internasionale standaarde in centipoise (cP) te meet. Daar is van drie metodes gebruik gemaak om die teenwoordigheid van leukositospermie in 'n semenmonster te ondersoek. Die eerste metode was die sitologiese metode waar die teenwoordigheid van granulosiet op die gekleurde semensmeer tydens die standaard morfologie beoordeling bepaal word. Die tweede was deur middel van 'n leukosietperoksidase toets waarmee daar 'n kwantitatiewe telling gedoen kan word, soos teenwoordig in 'n voorbereide semenmonster. Hierdie twee bepalings is op die totale studiepopulasie van 200 pasiënte gedoen. Die viskositeit van monsters met of sonder die teenwoordigheid van leukositospermie, soos bepaal met die voorafgaande metodes en gebaseer op die WGO riglyne, is met mekaar vergelyk. Korrelasies is ook tussen hierdie twee veranderlikes en verskeie semenparameters van hierdie twee groepe gedoen. Die derde metode was 'n biochemiese ontleding met behulp van 'n ensiemgekoppeldeimmuunsorberende essai (ELISA) vir die bepaling van die ekstrasellulêre konsentrasie van polimorfonukleêre (PMN) elastase ensiem in die seminale plasma. Hierdie toets is op 124 lukraak gekose semenmonsters uitgevoer. Alle monsters is gefraksioneer voor berging in vloeibare stikstof om meervoudige analises van elke monster moontlik te maak. Die PMN elastase konsentrasies is vergelyk met die viskositeit van die semenmonsters vir 'n moontlike korrelasie en verwantskap met die teenwoordigheid van leukositospermie. Die resultate van al drie hierdie metodes, vir die moontlike bepaling van infeksie, het 'n betekenisvolle positiewe verwantskap met die toename in graad van viskositeit in semenmonsters aangetoon. Die tweede benadering van hierdie studie was om die viskositeitsgradering en die kwantitatiewe leukositopermie waardes te vergelyk met die semenparameters wat bepaal is tydens die semenanalise. Die doel van hierdie benadering was om enige verwantskap of effek van viskositeit asook die teenwoordigheid van witbloedselle op die semenparameters te ondersoek. Daar is betekenisvolle verwantskappe gevind tussen die viskositeitstatus van 'n semenmonster, die teenwoordigheid van witbloedselle en die semenparameters, soos motiliteit, morfologie en spermatosoa konsentrasie. Die derde benadering was om 'n ondersoek te doen na die moontlike verwantskap tussen viskositeit en die sekretoriese funksies van die manlike bykomstige geslagskliere, te wete die prostaat en seminale vesikula. Die biochemiese ondersoek na die sekresies van hierdie twee organe, naamlik fruktose en sitroensuur, is gedoen om te bepaal of die teenwoordigheid van infeksies van die manlike traktus, en waargeneem as leukositospermia, ook in verband gebring kan word met die viskositeitstatus van 'n semenmonster. Daar is geen verband gevind tussen die sekresies van hierdie twee kliere en die viskositeit van die semenmonsters nie. Aangesien hierdie deel van die studie net as 'n loodsprojek beskou is, is die biochemiese bepalings slegs op 'n beperkte aantal semenmonsters uitgevoer en kan hierdie tipe ondersoek as 'n moontlike verdere studie onderneem word. Hierdie navorsingsresultate kan lei tot ‗n meer omvattende assessering van mans se fertiliteitstatus. Dit is uiters noodsaaklik in die konteks van omstandighede van die pasiënte wat die andrologielaboratorium van die Tygerberg Akademiese Hospitaal besoek aangesien die meerderheid nie gevorderde in vitro behandeling kan bekostig nie. Die akkurate bepaling van 'n semenmonster se viskositeit kan dus moontlik waarde toevoeg tot die identifisering, diagnose en behandeling van pasiënte met leukositospermie om sodoende hulle fertiliteitspotensiaal te verbeter.

Philosophiae Doctor - PhD
The sexual behaviour of youths is believed to play a role in the spread of SexuallyTransmitted Infections (STIs) and Reproductive Tract Infections (RTIs). This study examinesthe determinants of youth sexual behaviours and knowledge of reproductive tract infections (RTIs) and sexually transmitted infections (STIs) in Malawi. It explores rural/urbandifferentials in sexual behaviours using indicators such as early sexual initiation, multiplesexual partnerships, and non-use of condoms, in order to establish policy recommendationstoward improving sexual behaviour among youths. The Malawi Demographic Health Survey2010 data was used. Out of a sample of 2987 males and 9559 females aged 15-24 years,5652 females and 1405 males (condom use), 675 females and 511 males (inconsistentcondom use), 6470 females and 2026 males (multiple sexual partnerships (MSP)), and 15217females and 1405 males (early sexual debut) were filtered in the study.Chi-square and logistic regression techniques were performed to test for association betweensexual behaviour indicators and socio-demographic variables. The prevalence of non-use ofcondom was higher among catholic females (OR=1.11), lower among Muslim males (OR=0.81) and higher among CCAP females (OR=1.19). Muslim females were (OR=1.42) more likely to initiate sexual activities early, while Muslim males were (OR= 0.57) less likelyto initiate sexually activities early. Females in the central region (OR=1.51) and catholicmales (OR=1.63) were more likely to have more sexual partners.Encouraging these young people to be faithful to one uninfected partner, abstinence fromsexual activities, use condoms consistently and delay sexual initiation will help curb the spread of STIs in Malawi.

Includes bibliographical references
Integration is an important emerging health systems issue, which has relevance to different health programmes. Improving prevention of mother-to-child transmission of HIV (PMTCT) programs in South Africa would reduce preventable maternal and infant morbidity and mortality, assist with achieving Millennium Development Goals 4 and 5, and help in the response to the WHO call for the elimination of MTCT, the new international PMTCT goal. Integrating PMTCT care into routine maternal and child health programmes has been recommended as a way to optimize PMTCT care. The Part B literature review in this dissertation examines the reasons why PMTCT programmes need to engage with integration as an issue, challenges to implementing integrated programmes, followed by a discussion of the benefits and lessons to consider in planning integrated PMTCT programmes. Theoretical concepts and frameworks such as Atun's framework, complexity, Theory of Change and innovation in health systems are discussed, as they have key relevance to the research findings. Lessons about implementing health system changes can be learned from programmes which have done so successfully. Using Case Study methodology, the process of developing the fully integrated longitudinal clinic at McCord Hospital is described in Part C, and reflections on the experience of providing integrated care are captured through qualitative interviews with the staff. Recommendations regarding innovation and change within complex systems are made, emphasizing the need to understand contexts which are receptive to change and the importance of leadership in managing change.

Includes bibliographical references
Proper implementation of and adherence to antiretroviral therapy (ART) is significantly associated with better health and longer life in HIV-positive individuals. Consistent, adequate adherence has been shown to lead to a suppressed viral load. A low viral load delays the virus's progression and leads to better health outcomes for the individual. Adequate adherence is especially important among HIV-positive pregnant women. How well a woman adheres to her ART can not only improve her health during pregnancy but can protect the infant from HIV by preventing in utero transmission of the virus. Continuing ART protects against transmission via breastmilk later in the infant's life. While the benefits of good adherence are undeniable, the definition of adequate adherence varies widely in the literature. Taking 80 to 100% of pills as prescribed is commonly used as the threshold for adequate adherence levels. Various methods exist for measuring ART adherence, and while some are more reliable than others, there is no gold standard. This ambiguity in ART research extends to pregnant women, with even less known about HIV infected women established already on ART who then become pregnant. Changes in treatment protocols in the Western Cape and improvement of ART delivery throughout South Africa have resulted in this group of long-term users growing in size. Without more research into the barriers of ART adherence in these women, efforts to scale up treatment programs and to end mother to child transmission of HIV will ultimately fail. This dissertation is an exploration of these ideas. It begins to fill the gap in current knowledge related to ART compliance in pregnant women, and gives new insights into how specific barriers to adherence can adversely affect this specific group of established ART users.

Includes bibliographical references
BACKGROUND: A viral load monitoring algorithm in the 2013 Western Cape Department of Health PMTCT guidelines include VL measurement in women who are antiretroviral (ART)-experienced at presentation for antenatal care, the timing of subsequent VL measurements and criteria for regimen change. The study evaluates the implementation of the algorithm in women who are virologically nonsuppressed and determines the outcomes of virological resuppression and infant PCR status. METHODS: This retrospective cohort study focused on all ART-experienced women who presented for antenatal care at one of two primary level Maternity Obstetric Units (MOUs) in Khayelitsha, Cape Town between July 2013 and June 2014. The study used routine data from facility registers, clinical records and electronic monitoring systems at the MOU, and referral ART sites and hospitals. Data collected included age, ART clinic, start date and regimen, and maternal VL and infant PCR results. RESULTS: Forty percent of the 1412 HIV-positive pregnant women, were ART-experienced, of whom 14.1 % were VNS. Predictors of being VNS included a duration on ART of more than 4 years (p= 0.04), attending an ART clinic other than that in the facility (p= 0.02), being on a second-line ART regimen (p=0.07) and being younger than 25 years (p= 0.05). The algorithm was correctly followed in up to 87.5% of women identified as VNS. The rate of virological resuppression by three months postpartum was 70.0% to 82.3%. Excluding three neonates who died, all of the 82.2% of infants tested were PCR negative. CONCLUSIONS: Nearly 15% of ART-experienced women were virologically nonsuppressed on presentation for antenatal care. Levels of adherence to the guideline, and virological resuppression rates of up to 82.3% are encouraging. The implementation of the VLM algorithm could be improved by the integration of obstetric and ART care, the adoption of a single electronic monitoring system and the use of standardised integrated clinical stationery.

Background: Intimate Partner Violence (IPV) is recognized globally as a major public health concern linked to numerous adverse physical, mental, sexual and reproductive health outcomes. IPV is associated with both pregnancy and HIV-infection independently, but there are few data on IPV in populations of HIV-infected pregnant women. We examined the prevalence and predicators of IPV among pregnant women initiating lifelong antiretroviral therapy (ART) in a large primary care clinic in Cape Town, South Africa. Methods: Consecutive pregnant women seeking antenatal care in Gugulethu, Cape Town were recruited into the MCH-ART study examining service models for postpartum ART care. IPV, depression, alcohol and drug use, and emotional distress were assessed using the 13-item WHO Violence Against Women questionnaire, the Edinburgh Postnatal Depression Scale (EPDS), alcohol and drug use disorders identification test (AUDIT/DUDIT) and the Kessler-10 (K-10) scale, respectively. Questionnaires were administered privately by trained interviewers. Women identified with specific IPV or mental health concerns were referred to appropriate services. Logistic regression was used to examine factors independently associated with experiences of IPV after adjusting for age and socioeconomic status. Results: From April 2013-May 2014, 623 women were enrolled (median age, 28 years):97% reported being in a relationship, 38% were married and/or cohabiting and 70% reported not having discussed or agreed on pregnancy intentions prior to conception . Overall, 21%(n=132) reported experiencing ≥ 1 act of IPV in the past 12 months, including emotional violence(15%), physical violence(15%) and sexual violence(2%). Of those reporting any IPV, 48% reported experiencing multiple types. Emotional and physical violence were most prevalent among women 18-24 years old, while sexual violence was most commonly reported among women 25-29 years old. Women who reported not discussing or disagreeing on pregnancy intentions with their partners prior to conception were significantly more likely to experience violence(p=0.030), and women who experienced IPV reported higher levels of substance abuse, depression and emotional distress(p<0.001 for all associations). Discussion: These data demonstrate high levels of IPV in this population. While the potential impact of HIV-infection, pregnancy and pregnancy intention on the risk of IPV and related factors require further research, IPV-related screening and support services should be considered as part of the package of care for ART in pregnancy.

Introduction: Malaria and curable sexually transmitted and reproductive tract infections (STIs/RTIs) are important causes of adverse birth outcomes (ABO) and are both prevalent in most parts of sub-Saharan Africa. From a public health perspective, control of these infections requires interventions that are part of an integrated antenatal care package. The extent to which there may be coinfection increases the importance of such an integrated approach to reduce ABO. A systematic review and meta-analysis published in 2012 showed that the prevalence of malaria and curable STIs/RTIs among antenatal attendees in sub-Saharan Africa is considerable. However, the prevalence of malaria and curable STI/RTI coinfection has not been reported in any epidemiological setting. The primary objective of this thesis is to address this knowledge gap by estimating the prevalence of malaria, curable STIs/RTIs and their coinfection and to highlight the importance of an integrated approach to control malaria and STIs/RTIs in pregnancy. Secondary objectives of the study were to: (1) determine risk factors for malaria, curable STIs/RTIs and their coinfection; (2) estimate the prevalence of ABO and identify risk factors for ABO; (3) measure the in vivo efficacy and the prophylactic effect of sulphadoxine-pyrimethamine (SP) in pregnant women, and (4) characterise the molecular markers associated with parasite resistance to SP among pregnant women. Methods: A prospective cohort study of 1,086 antenatal attendees was conducted in Nchelenge District, Zambia. Consenting women visiting two health centres for their first antenatal care (ANC) visit were screened for malaria and curable STIs/RTIs (Chlamydia, gonorrhoea, trichomoniasis, bacterial vaginosis [BV] and syphilis). Socio-demographic data and maternal characteristics were also collected at enrolment. Sulphadoxine-pyrimethamine was administrated as intermittent preventive treatment to eligible women and they were followed up at day 28 for a second 13 malaria screening to determine the therapeutic and prophylactic failure of SP. At delivery participants were screened for placental malaria and data on birth outcomes were recorded. Univariate and multivariate analyses were conducted to determine the association between the potential risk factors for infection and ABO. Results: Of the 1086 women recruited 729 were successfully followed to delivery. The prevalence of malaria infection measured by microscopy was 31.8% (95% CI, 29.1-34.6) and by PCR was 57.8% (95% CI, 54.9-60.8). The risk of malaria infection was higher among pregnant women recruited from Nchelenge health centre compared to those attending the Kashikishi health centre (adjusted odds ratio [aOR] = 1.81; 95% CI, 1.38-2.37, P < 0.001), and HIV-infected women across health centres had a greater risk of malaria infection compared to HIV-uninfected women (aOR = 1.46; 95%, 1.00-2.13, P = 0.045). Infection with at least one STI/RTI was observed in 64.8% (95% CI, 61-67.4) of the participating women. With the exclusion of BV the prevalence of infection with at least one curable STI was 34.5% (95% CI, 31.7-37.4). Infection with at least one STI was associated with BV. In comparison to uninfected women, women infected with BV were at a higher risk of being infected with at least one STI (aOR 1.44; 95% CI, 1.08-1.92, P = 0.012). HIV-infected women had a higher risk of infection with BV than HIV-uninfected women (aOR 1.87; 95% CI, 1.24-2.83, P = 0.003) and women infected with at least one STI had a higher risk of BV (aOR 1.40; 95% CI (1.07 -1.84, P = 0.01). Among participants with complete results (n=1071), 38.7% (95% CI,35.7-41.6) were coinfected with malaria parasites and at least one STI/RTI; 18.9% (95% CI, 16.5-21.2) were infected with malaria parasites only; 26.0% (95% CI, 23.5-28.8) were infected with at least one STI/RTI but no malaria parasites, and 16.4% (95% CI, 14.1-18.6) had no infection. The risk of malaria and curable STI/RTI coinfection was higher among HIV infected women than HIV-uninfected women (OR; 3.59 [95% CI, 1.73-7.48], P < 0.001). The prevalence of composite ABO was 35.1%. Women shorter than 1.5m were at a higher risk of experiencing at least one ABO (aOR 1.55; 95% CI, 1.10-2.18, P = 0.02). The risk of having ABO among para II was less than half of the risk observed in 14 primiparous women (aOR 0.41; 95% CI, 0.27-0.61, P < 0.001) and much lower among multiparous women (aOR 0.32; 95% CI, 0.22-0.48, P < 0.001). Having taken two or more doses of SP during pregnancy was protective against ABO (aOR 0.47; 95% CI, 0.31-0.72, P = 0.001). None of the infections (malaria, curable STIs/RTIs and their coinfection) diagnosed at first ANC were associated with ABO. The prevalence of highly resistant quintuple mutant was 68.8% among first ANC attendees. Despite the moderate prevalence of the quintuple mutant among pregnant women, SP cleared parasitaemia in 86% of the asymptomatic malaria cases among HIV-negative women Conclusion: The prevalence of malaria, STI/RTI and their coinfection at first ANC in this study population was considerable. However, no association was found between ABO and infection with malaria or STI/RTI or their coinfection. This lack of association is partially a result of interventions within the ANC package including treatment of some STI/RTI, intermittent preventive treatment in pregnancy with SP and iron and folic acid supplementation. Sulphadoxine-pyrimethamine retains partial efficacy against P. falciparum malaria in this area with moderate prevalence of the quintuple mutant. While continuing the policy of offering intermittent preventive treatment with SP during pregnancy, an alternative preventive therapy that is effective against both malaria and STIs/RTIs needs to be considered.

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Multivariate statistical analysis was used for environmental groupings in Cerrado and Caatinga evaluating the relationship between positive serological prevalences for brucellosis, bovine viral diarrhea (BVD), infectious bovine rhinotracheitis (IBR), leptospirosis, enzootic bovine leukosis (EBL), neosporosis and toxoplasmosis in bovine Curraleiro Pé-Duro, associated with socioeconomic data of the municipalities. Serological results were obtained from the Pro-Centro-Oeste Network database; socioeconomic variables of IBGE and environmental data of the Laboratory of Image Processing and Geoprocessing of UFG and National Institute of Meteorology, in two periods 2006 and 2011. Environmental variables were grouped, later was performed discriminant analysis and canonical correlation. In 2006, cluster 1 was located in the Cerrado-Amazonian transition area and were associated the prevalences of brucellosis, leptospirosis, EBL, IBR and BVD; Cluster 2 was characterized by vegetation typical of Cerrado and was related the prevalence of neosporosis and toxoplasmosis; Cluster 3 was differentiated by water stress and presented the intermediate values of prevalence; Cluster 4 was characterized by areas for environmental protection of the native vegetation; and cluster 5 constituted an anthropogenic environment in the Cerrado. In 2011, cluster 1 was characterized by Cerrado regions rich in natural vegetation and Caatinga, warmer, lower rainfall and low altitudes were associated with the prevalences of LEB, IBR and BVD; Cluster 2 in dry regions associated with the prevalence of neosporosis; Cluster 3 Cerrado antropizado with more hot and humid climate, higher rainfall at high altitudes related to the prevalence of leptospirosis and brucellosis, in dairy cattle. Evaluation of the landscape in the prevalence of bovine diseases reflects historical and socioeconomic aspects of agriculture.
Análise estatística multivariada foi utilizada para agrupamentos ambientais, em Cerrado e Caatinga avaliando a relação entre prevalências sorológicas positivas para brucelose, diarreia viral bovina (BVD), rinotraqueíte infecciosa bovina (IBR), leptospirose, leucose enzoótica bovina (LEB), neosporose e toxoplasmose de bovinos Curraleiro Pé-Duro, juntamente com dados socioeconômicos dos municípios. Resultados sorológicos foram obtidos do banco de dados da Rede Pró Centro-Oeste; socioeconômicos do IBGE e ambientais da plataforma de dados do Laboratório de Processamento de Imagens e Geoprocessamento da UFG e Instituto Nacional de Meteorologia, em dois períodos 2006 e 2011. Variáveis ambientais foram agrupadas, posteriormente foram realizadas análise discriminante e correlação canônica. Em 2006, cluster 1 localizou-se em área de transição Cerrado-Amazônia e associou-se as prevalências de brucelose, leptospirose, LEB, IBR e BVD; Cluster 2 caracterizou por vegetação típicas de Cerrado e relacionou-se as prevalências de neosporose e toxoplasmose; Cluster 3 diferenciou-se pelo estresse hídrico e apresentou os valores intermediários de prevalências; Cluster 4 caracterizou por áreas para proteção ambiental da vegetação remanescente; e cluster 5 constituiu-se ambiente antropizado no Cerrado. Em 2011, cluster 1 caracterizou-se por regiões de Cerrado ricas em vegetação natural e Caatinga, mais quentes, menor pluviometria e baixas altitudes associaram-se as prevalências de LEB, IBR e BVD; Cluster 2 regiões mais secas associadas a prevalência de neosporose; Cluster 3 Cerrado antropizado com clima mais quente e úmido, maior pluviosidade em elevadas altitudes relacionados as prevalências de leptospirose e brucelose, na pecuária leiteira. Avaliação da paisagem na prevalência de doenças bovinas reflete aspectos histórico e socioeconômico da agropecuária.

Chlamydia is the most reported sexually transmitted infection in the US and is caused by the obligate intracellular bacterium Chlamydia trachomatis. Typically, this presents as a lower genital tract infection (cervicitis or urethritis), but can ascend to the upper genital tract, causing pelvic inflammatory disease, tubal infertility, epididymitis, or ectopic pregnancy. While chlamydia infections can be cured with a single-dose oral antibiotic, repeat infections are common and having multiple chlamydial infections increases a woman’s risk of developing serious chronic conditions. Previous research has shown that estrogen has a positive effect on C. trachomatis infections—an important finding, connecting fluctuating estrogen levels in females to variance in pathogenesis.The mechanism behind this hormonal influence remains unknown; however, previous work in our laboratory indicates that estrogen-stimulated stromal cell effectors play a role in enhancing C. trachomatis infections in a polarized endometrial epithelial Ishikawa (IK)/stromal (SHT-290) cell co-culture model. Specifically, our data indicate that estrogen exposure stimulates osteopontin and vimentin release from stromal cells in co-culture with endometrial epithelial cells. Furthermore, we noted that Chlamydia-infected, polarized Ishikawa cells exposed to a combination of recombinant osteopontin and estrogen released significantly more infectious chlamydia than cultures exposed to estrogen alone. Most tissue culture models being used today employee non-polarized cells. Given the fact that epithelial cell polarization is known to impact C. trachomatis serovar E development, in the current study we sought to determine if the estrogen-induced stromal cell effectors, osteopontin and vimentin, affect C. trachomatis viability and infectivity in non-polarized Ishikawa cells. Non-polarized Ishikawa cells were exposed to osteopontin or vimentin in the presence or absence of estrogen, infected with C. trachomatis serovar E, and collected for examination of chlamydial infectivity and progeny production. Our initial data show that osteopontin and vimentin impact chlamydial progeny production in a concentration dependent fashion, with higher concentrations of recombinant effectors +/- estrogen significantly decreasing progeny production. These data suggest that polarization of host cells influences the way hormone-stimulated effectors interact with the cell to impact on chlamydial infection. Future research goals are to explore other stromal effectors such as fibronectin with estrogen and to study the cell signaling mechanism osteopontin and vimentin use to affect chlamydial infections in polarized epithelial cell cultures.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior
RESUMO O surgimento do HIV/aids e o delineamento da epidemia demandaram mudanÃas para a saÃde sexual e reprodutiva de homens e mulheres que (con) vivem com o vÃrus. A sobrevida e a qualidade de vida melhoradas com o aparecimento da terapia antiretroviral combinada colocou em destaque o aspecto de cronicidade da infecÃÃo pelo HIV, delineando possibilidades de relaÃÃes afetivo-sexuais e reprodutivas, mediante esta nova realidade, num panorama complexo que envolve casais soroconcordantes e sorodiscordantes em contextos de vida similares aos nÃo-infectados, num processo de re-significaÃÃo do HIV/aids e de busca pelo controle dessa pandemia. Este estudo teve como objetivo compreender vivÃncias sexuais e reprodutivas de pessoas que (con) vivem com HIV. A Teoria HumanÃstica de Enfermagem de Paterson e Zderad foi utilizada como referencial teÃrico-metodolÃgico. Trata-se de uma pesquisa descritiva com delineamento qualitativo, realizada no ambulatÃrio de infectologia do Hospital-Escola Santo InÃcio, em Juazeiro do Norte-CE. Os sujeitos do estudo foram 16 pessoas que (con) vivem com HIV/aids, 7 homens e 9 mulheres. Os dados foram coletados nos meses de julho a novembro de 2007, por meio de observaÃÃo livre, consulta aos prontuÃrios e entrevista semi-estruturada. Para anÃlise dos depoimentos foi adotada a tÃcnica de anÃlise de conteÃdo, de onde emergiram trÃs temÃticas: 1. VivÃncia Sexual; 2. VivÃncia Reprodutiva; e 3. VivÃncia da Conjugalidade. Nestas temÃticas, foram identificadas onze sub-temÃticas: 1. O preservativo nas relaÃÃes sexuais; 2. AlteraÃÃes no desejo apÃs a descoberta da soropositividade ao HIV; 3. AlteraÃÃes na prÃtica sexual apÃs a descoberta da soropositividade ao HIV; 4. MÃtodos contraceptivos usados antes da vivÃncia e convivÃncia com o HIV/aids; 5. O preservativo como referÃncia contraceptiva e de proteÃÃo nas relaÃÃes sexuais; 6. Desconhecimento do uso de outros mÃtodos contraceptivos na infecÃÃo pelo HIV; 7. Desejo de ter filhos; 8. Medo da transmissÃo vertical do HIV; 9. (Des)conhecimento das medidas profilÃticas na reduÃÃo da transmissÃo vertical do HIV; 10. ModificaÃÃo na relaÃÃo conjugal frente ao cuidado consigo e com o outro; 11. A quebra da confianÃa depositada no outro frente ao HIV. Das pessoas que vivem e convivem com HIV/aids foram apreendidas diferentes experiÃncias e significados para as vivÃncias sexuais e reprodutivas, em cenÃrios de vida complexos, ainda permeados pelos estigmas decorrentes da aids. Os sujeitos deste estudo viviam em uniÃo conjugal variando de oito meses hà mais de quinze anos, dos quais onze viviam em relaÃÃo conjugal soroconcordante ao HIV e cinco em relaÃÃo sorodiscordante. NÃo percebemos divergÃncia de dados pela variÃvel tempo de uniÃo. Verificamos situaÃÃo sÃcio-econÃmica precÃria e presenÃa de filhos, dos quais cinco concebidos apÃs o conhecimento do status sorolÃgico, e mais duas mulheres no perÃodo gestacional. O tempo de convivÃncia com a infecÃÃo foi variÃvel, de menos de um ano a mais de onze anos. Em metade dos casos o contexto de descoberta da infecÃÃo pelo HIV envolveu o perÃodo gestacional, sendo os outros apÃs doenÃa oportunista ou por convocaÃÃo de parceiro, revelando-se como um momento difÃcil pela infidelidade conjugal comprovada. Os resultados indicaram que o preservativo nÃo fazia parte da rotina sexual atà o conhecimento do status sorolÃgico, sendo essa condiÃÃo determinante para a adesÃo ao preservativo masculino. A estabilidade da relaÃÃo conjugal atuava, na fase prÃ-infecÃÃo, como um dos fatores que contribuÃa para a determinaÃÃo do nÃo uso de preservativo, oferecendo contextos de maior vulnerabilidade, onde o gÃnero aparece como principal fator. O uso do preservativo masculino, apÃs a soroconversÃo, evidenciou as dificuldades nessa adesÃo, principalmente entre os que nunca haviam experienciado esse mÃtodo de proteÃÃo, revelando possÃvel consciÃncia para a necessidade de adaptaÃÃo ao dispositivo na relaÃÃo sexual, que se mostra re-significada para essas pessoas. Contudo, hà um enfrentamento maior para a manutenÃÃo da prÃtica de prevenÃÃo pelo uso do preservativo masculino em casais sorodiscordantes. A descoberta da soropositividade ao HIV demandou modificaÃÃes na rotina sexual, evidenciando a diminuiÃÃo do desejo sexual e alteraÃÃo nas prÃticas sexuais, com distintos aspectos entre homens e mulheres pesquisados. Foram expressas mudanÃas no uso rotineiro dos mÃtodos contraceptivos anterior à soroconversÃo, com a utilizaÃÃo de novos mÃtodos, notadamente o preservativo masculino, frente à presenÃa do HIV. Evidenciamos o desconhecimento de alternativas anticonceptivas diante da infecÃÃo pelo HIV e da aids. O desejo de ter filhos foi observado em homens e mulheres, onde o medo da transmissÃo vertical aparece como forte determinante em abolir essa escolha, com o desconhecimento de medidas profilÃticas na reduÃÃo da transmissÃo vertical. As dificuldades no enfrentamento do HIV/aids impÃem mudanÃas no cotidiano da conjugalidade, destacando um comportamento conjugal bilateral de cuidado com o outro em uma relaÃÃo ambÃgua frente à confianÃa quebrada exposta com o conhecimento do status sorolÃgico. Este estudo nos permitiu perceber que à preciso abrir canais de diÃlogo sobre experiÃncias sexuais e reprodutivas, salientando a importante dimensÃo que à conferida Ãs relaÃÃes entre profissionais e pacientes, como partÃcipes na busca da promoÃÃo da saÃde numa realidade em construÃÃo, de re-significaÃÃo de vida, relaÃÃes e saÃde. Evidencia-se o perÃodo gestacional como um importante momento para o diagnÃstico da infecÃÃo pelo HIV, para aconselhamento das recomendaÃÃes para reduÃÃo da transmissÃo vertical, com inicio precoce da profilaxia da transmissÃo vertical, num atendimento humanizado, livre de julgamentos e preconceitos. A assistÃncia em saÃde sexual e reprodutiva Ãs pessoas vivendo com HIV demanda inÃmeras questÃes e desafios, mas, sobretudo, aponta para a necessidade da assistÃncia integral, nÃo-dicotÃmica, onde prevenÃÃo e tratamento se conjugam, reconhecendo limites, possibilidades, finalidades e prioridades, na individualizaÃÃo do cuidado humano.
ABSTRACT The arise of HIV/AIDS and the design of the epidemy demanded changes in the sexual and reproductive health of men and women who live with the virus. The fact that survival and life quality improved with the advent of antiretroviral therapy highlighted the aspect of chronicity of HIV infection, outlining possibilities for affective-sexual and reproductive relationships in this new reality, in a complex scenery that involves concordant and discordant couples in contexts of life similar to non-infected people, in a process of re-signification of HIV/AIDS and of search for control of this pandemy. This study aimed to understand sexual and reproductive experience of people who live with HIV. The Humanistic Nursing Theory by Paterson and Zderad was used as a theoretical and methodological reference. This is a descriptive research with qualitative design, held at the infectology clinic of the School Hospital Santo InÃcio, in Juazeiro do Norte-CE. The subjects of the study were 16 people who live with HIV/AIDS, 7 men and 9 women. Data were collected from July through November, 2007, through free observation, analysis of medical records and semi-structured interview. For the testimoniesâ analysis the technique of content analysis was adopted, from which emerged three themes: 1. Sexual experience; 2. Reproductive experience, and 3. Marriage Experience. In these themes one identified eleven sub-themes: 1. The condom in sexual intercourses; 2. Changes in desire after the discovery of HIV seropositivity, 3. Changes in sexual practice after the discovery of HIV seropositivity, 4. Contraceptive methods used before the experience and living with HIV/AIDS; 5. The condom as a contraceptive reference and protection in sexual intercourses; 6. Ignorance about the use of other contraceptive methods in HIV infection; 7. Desire to have children; 8. Fear of vertical transmission of HIV; 9. (Lack of) knowledge about prophylactic measures to reduce the vertical transmission of HIV; 10. Modification in marital relationship due to self-care and care with the other; 11. The distrust in the partner because of HIV. Out of the people who experience and live with HIV/AIDS one got different experiences and meanings for sexual and reproductive experiences in complex life sceneries, still permeated by the stigma resulting from AIDS. The subjects of this study lived in marital union ranging from eight months through over fifteen years, eleven of whom lived in conjugal concordant relationship to HIV and five in discordant relationship. We did not notice divergence of data by the variable time of union. We noticed difficult socioeconomic situation and presence of children, including five conceived after the knowledge of HIV, and two women during pregnancy. The time spent living with the infection varied from less than a year to more than eleven years. In half the cases the context of discovery of HIV infection involved the gestational period, the others after opportunistic disease or by convincing of the partner, being a difficult moment due to proved marital infidelity. The results indicated that the condom was not part of their sexual routine until the knowledge of HIV, being the virus a determinant condition for joining the condom. The stability of the conjugal relationship served in the pre-infection phase as one of the factors that contributed to the non-use of condoms, causing larger contexts of vulnerability, where the genre appears as the main factor. The use of male condoms, after seroconversion, highlighted the difficulties in adhesion, especially among those who had never experienced this method of protection, revealing possible awareness of the need to adapt to the device in sexual intercourse, which is re-signified for these people. However, there is a bigger confrontation for the maintenance of the prevention practice by the use of condoms in discordant couples. The discovery of HIV seropositivity demanded changes in sexual routine, showing a decrease in sexual desire and change in sexual practices, with different aspects for men and women surveyed. There were changes in routine of contraceptive methods used before the seroconversion, using new methods, especially the male condom, in the presence of HIV. We highlighted the lack of knowledge of alternatives contraceptive methods face to HIV infection and AIDS. The desire to have children was observed in men and women, and the fear of vertical transmission appears as a strong determinant to deny that choice, with the lack of prophylactic measures to reduce vertical transmission. The difficulties in fighting against HIV/AIDS require changes in the daily life of the couple, highlighting a bilateral marital behavior of care for the other in an ambiguous relationship because of distrust with the knowledge of HIV infection. This study allowed us to realize that we must open channels of dialogue about sexual and reproductive experiences, stressing the important dimension that is given to the relationships between professionals and patients, as participants in the search of health promotion in a reality still in construction, of re-signification of life, of relationships and health. The gestational period is highlighted as an important moment for the diagnosis of HIV infection, to advise the recommendations and to reduce vertical transmission, beginning with early prevention of vertical transmission, through humanized care, free of judgments and prejudice. The assistance in sexual and reproductive health for people living with HIV demands several questions and challenges, but it points mainly to the need of integral and non-dichotomous assistance, where prevention and treatment work together, recognizing limits, possibilities, aims and priorities, in the individualization of human care.

Alors que les politiques de santé sont passées au cours des dix dernières années d'un traitement de la procréation en contexte VIH comme une « exception » à un discours de « normalisation », la thèse vise à comprendre les conditions et les effets de cette évolution. L'enquête ethnographique a été conduite sur une période de dix ans auprès de personnes vivant avec le VIH sous thérapie antirétrovirale, de femmes vivant avec le VIH ayant eu une expérience de procréation, et de professionnels de santé intervenant en PTME dans deux structures de santé de la reproduction au Sénégal. Cette étude met en lumière un « système moral » de la prévention du VIH, contradictoire à certains égards, qui offre aux femmes peu de moyens socialement acceptables pour se protéger du risque VIH. La procréation peut être perçue comme une stratégie pour réaffirmer une identité féminine, tester la capacité d'un corps « normalisé » par les ARV à enfanter sans transmettre le VIH, raffermir les liens conjugaux en souffrance et réduire les risques de stigmatisation sociale. Ces logiques ne sont pas toujours comprises par des professionnels de santé « spécialistes du VIH » souvent débordés dans la prise en charge médicale et psychosociale des PvVIH, qui soutiennent peu ces processus. Les hommes vivant avec le VIH apparaissent isolés, fragiles, voire « oubliés » . Ce travail montre les multiples usages sociaux de la procréation : objet d'émulation, de résistance, de souffrance et de rivalité pour les femmes VIH et leurs conjoints. Parallèlement à la normalisation « décrétée » par les instances de santé publique, les femmes vivant avec le VIH se sont réapproprié la possibilité de procréer
Since the last decade has seen a transition from treating childbearing in the context of HIV as an “exception” to a discourse of “normalization,” this dissertation aims to understand the conditions and effects of this change. This ethnographic survey was conducted over a period of ten years among people living with HIV receiving antiretroviral therapy, women living with HIV who experienced childbearing and healthcare professionals working in PMTCT in two reproductive health facilities in Senegal. This study sheds lights on a “moral system” for HIV prevention, contradictory in some respects, that provides women few socially acceptable means to protect themselves from the risk of HIV. Childbearing may be perceived as a strategy to reaffirm female identity, test the capacity of a body made “normal” by ARVs to give birth without transmitting HIV, strengthening strained marital bonds, and reducing the risk of social stigmatization. Men living with HIV appear isolated, fragile, unsupported, and even “forgotten” relative to childbearing while they themselves are suffering or are affected by the situations of their wives or families. Health professionals now integrate HIV counseling and testing in their practices but continue to project attitudes of “exception” about treating PLHIV and pregnant HIV-Positive women. This study shows the various social uses of childbearing : a subject leading to emulation, resistance, suffering, and rivalry for women living with HIV and their spouses. Alongside the normalization “decreed” by public health officials, women living with HIV have reclaimed the possibility to procreate

Hospital-acquired infections (HAI) are not uncommon in healthcare facilities. They are usually prevented by sanitation techniques and by maintaining a high standard of care. Catheter-associated urinary tract infections (CAUTI) make up a large percentage of hospital-acquired infections and are often the most preventable type of HAI. Patterns in infection rate could provide new ideas on prevention techniques, which might further reduce infection rate, saving lives and cutting costs. CAUTI infection rate was measured from January KJIY to September KJIL and was differentiated based on hospital ward as well as month and season. Overall, ICU units tended to have a higher CAUTI infection rate than ward units, particularly in January, February, April, and May. The CAUTI infection rate was highest in the ICU units during spring and May, and lowest during fall and October. In the ward units, the CAUTI infection rate was highest during summer and March, and lowest during winter and February.

La répartition des taux de prévalence des infections transmissibles sexuellement et par le sang (ITSS) et du VIH/SIDA au Canada présente de grandes inégalités entre les différents groupes socioculturels. Les Autochtones font partie des populations qui en payent le plus lourd tribut. Par rapport à cette situation, le plan directeur 2007-2017 de la commission de la santé et des services sociaux des Premières Nations du Québec et du Labrador (CSSSPNQL) identifie clairement le VIH/SIDA comme une problématique prioritaire de santé. La stratégie autochtone sur le VIH/SIDA estime que pour être efficaces, les interventions visant la prévention du VIH/SIDA doivent cibler divers groupes, au nombre desquels la jeunesse autochtone est une cible particulière. En ce sens, la familiarité des jeunes générations avec la technologie positionne l’utilisation des technologies de l’information et de la communication (TIC) comme une avenue fortement prometteuse dans le domaine de la prévention du VIH/SIDA chez les adolescents et jeunes adultes. Nous avons réalisé une synthèse des connaissances dans ce domaine novateur suivant une méthodologie suggérée par la Collaboration Cochrane dans le but de documenter l’efficacité et les facteurs d’adoption des interventions utilisant les TIC pour la prévention des ITSS/VIH/SIDA et la promotion de la santé sexuelle et reproductive auprès des adolescents et jeunes adultes. Les résultats de cette revue systématique ont permis d’élaborer et de mener, en partenariat avec la CSSSPNQL, un projet de recherche visant à évaluer la faisabilité de telles interventions au sein des adolescents et jeunes adultes de communautés des Premières Nations (PN) du Québec. En complément à cette étude de faisabilité et dans le but de formuler des recommandations en vue de la conception d’interventions utilisant les TIC et fondées autant sur les données probantes que sur les réalités des jeunes des PN, nous avons entrepris une dernière étude visant à identifier les facteurs sous-jacents du port du condom chez les 13-18 ans de communautés des Premières Nations du Québec. Nous avons discuté, dans la présente thèse, les résultats de ces études ainsi que divers enjeux du partenariat de recherche avec les parties prenantes des PN ayant participé à notre projet. Les implications pratiques de nos résultats, en matière de recherche et d’intervention, sont à discuter avec notre principale partenaire, la CSSSPNQL, afin d’en optimiser les retombées pour les populations des PN.
The distribution of sexually transmitted infections (STIs) and HIV / AIDS prevalence in Canada presents large inequalities between different socio-cultural groups. Aboriginal people are, among the population, which pay the heaviest price. The First Nations of Quebec and Labrador Health and Social Services Commission (FNQLHSSC) has identified sexually transmitted infections, including HIV/AIDS, as a priority health issue. The Aboriginal Strategy on HIV / AIDS estimates that to be effective, interventions to prevent HIV / AIDS must target various groups, among which Aboriginal youth is a particular target. In this sense, the familiarity of the younger generation with technology positions especially the use of information and communications technology (ICT) as a highly promising avenue for HIV / AIDS prevention among adolescents and young adults. We conducted a knowledge synthesis in this innovative field following the methodology suggested by the Cochrane Collaboration to highlight the effectiveness and the adoption factors of interventions using ICT for the prevention of STIs/HIV/AIDS and for the promotion of sexual and reproductive health among adolescents and young adults. The results of this systematic review were used to develop and conduct, in partnership with the FNQLHSSC, a research project aiming at studying the feasibility of interventions using information and communication technologies (ICT) to promote sexual health among adolescents and young adults of Quebec First Nations (FN) communities. As a complement to this feasibility evaluation, a study was conducted in order to formulate exhaustive recommendations for the development of evidence-based interventions that also take into account the characteristics of the target population. This study aimed to identify the factors underlying condom use among 13-18 year olds from FN communities of Quebec. We discussed in this thesis the results of those studies, as well as various issues of our research partnership with the FN stakeholders who participated in our project. The practical implications of our results, in terms of research and intervention, are to be discussed with our main partner, the FNQLHSSC, in order to maximize benefits for the populations of PN.

Cette thèse examine les déterminants de la recherche d'information en santé sexuelle et reproductive (SSR) via Internet chez les adolescent-e-s âgé-e-s de 15 à 19 ans au Burkina Faso en se focalisant sur deux problématiques de santé : les grossesses non désirées et les infections transmissibles sexuellement et par le sang (ITSS). Sur le plan théorique, la thèse s'appuie sur un cadre théorique intégrateur. Ce modèle combine différentes variables issues de la théorie du comportement planifié, de la théorie du comportement interpersonnel et du modèle de recherche et de traitement d'information sur les risques. Il est utilisé pour expliquer l'intention de recherche d'information sur les grossesses non désirées et les ITSS via Internet chez ces adolescent-e-s. L'étude comportait d'abord un premier volet méthodologique qui a permis (i) d'identifier les croyances saillantes et modales des adolescent-e-s, (ii) d'évaluer la compréhension du questionnaire et (iii) de vérifier les qualités psychométriques de celui-ci. Le questionnaire final a été conçu à la suite des ajustements réalisés lors de ce volet de validation du questionnaire. Le second volet, qui est l'étude principale, a permis de collecter des informations sur les facteurs pouvant affecter la recherche d'information en SSR via Internet chez les adolescent-e-s concernant les grossesses non désirées et les ITSS. Au total, 730 adolescent-e-s ont participé à l'étude principale, dont 363 répondants pour le questionnaire portant sur les grossesses non désirées et 367 pour le questionnaire portant sur les ITSS. Dans le but d'identifier les déterminants de l'intention de recherche d'information via Internet sur les grossesses non désirées et les ITSS chez ces adolescent-e-s, plusieurs modèles d'analyses logistiques multivariées, stratifiés selon le sexe et selon la problématique de SSR (grossesses non désirées et ITSS), ont été estimés. Les résultats ont révélé que les facteurs déterminant l'intention de recherche d'information en SSR via Internet diffèrent selon le sexe et selon la problématique de SSR. Concernant l'intention de recherche d'information via Internet sur les grossesses non désirées, la variance expliquée du modèle final est de 38 % pour les garçons et 37,9 % pour les filles. Chez les garçons, les principaux déterminants de l'intention de recherche d'information via Internet sur les grossesses non désirées sont l'attitude cognitive (RC = 4,6; IC95% : 1,70 - 12,21), le comportement passé (RC = 5,5; IC95% : 1,93 - 15,85) et la norme subjective (RC = 3,2; IC95% : 1,34 - 7,43). Pour les filles, c'est l'attitude cognitive (RC = 23,3; IC95% : 2,40 - 32,68) qui apparaît comme le déterminant principal de l'intention. Concernant l'intention de recherche d'information via Internet sur les ITSS, la variance expliquée du modèle final est de 40,17 % pour les garçons et 33,28 % pour les filles. Chez les garçons, les principaux déterminants de l'intention de recherche d'information sur les ITSS via Internet sont l'attitude cognitive (RC = 6,8; IC95% : 2,13 - 21,46), l'attitude affective (RC = 3,6; IC95% : 1,42 - 9,14) et le comportement passé (RC = 3,3; IC95% : 1,19 - 9,10). Pour les filles, seulement des tendances statistiques ont été observées dans le modèle de prédiction de l'intention de recherche d'information en ligne sur les ITSS. Au regard de ces résultats, les stratégies de communication en santé visant à renforcer la recherche d'information en SSR via Internet par les adolescent-e-s au Burkina Faso devraient être ajustées pour intégrer ces déterminants afin d'améliorer leur efficacité. Bien que les résultats de cette thèse soutiennent des actions possibles en communication, l'amélioration de la SSR des adolescents au Burkina Faso impliquera une approche globale et intégrée de santé publique.
This thesis investigates the determinants of online information seeking about sexual and reproductive health (SRH) among adolescents aged 15-19 years in Burkina Faso by focusing on two health issues: unwanted pregnancies and sexually transmitted and blood-borne infections (STBBIs). Theoretically, the study is built on an integrative framework. This model combines variables from the planned behaviour theory, the interpersonal behaviour theory and the risk information search and processing model. It is used to explain the intention to seek information on unwanted pregnancy and STBBIs via the online among these adolescents. The study began with an initial methodological phase that enabled us to (i) identify adolescents' modal salient beliefs (ii) evaluate the questionnaires' comprehensibility and (iii) check its psychometric qualities. The final questionnaires were created based on adjustments made during this first phase. The second phase, which is the main study, collected information on factors affecting adolescents' online information seeking on unwanted pregnancies and STBBIs. A total of 730 adolescents were surveyed, 363 completing the questionnaire on unwanted pregnancy and 367 completing the one on STBBIs. To identify the determinants of adolescents' intention to seek online information on unwanted pregnancies and STBBIs, several multivariate logistic analysis models were estimated, stratifying by sex and by the SRH issue (unwanted pregnancies and STBBIs). The results from these estimations suggest that the determinants of the intention to seek SRH information online differ by sex and by SRH issue. Regarding the intention to seek information on unwanted pregnancies online, the explained variance of the final model is 38% for boys and 37.90% for girls. For boys, the main determinants of intention to seek information about unwanted pregnancies online are cognitive attitude (OR = 4.6; CI95%: 1.70 - 12.21), past behaviour (OR = 5.5; CI95%: 1.93 - 15.85) and subjective norm (OR = 3.2; CI95%: 1.34 - 7.43). For girls, cognitive attitude (OR = 23.3; 95% CI: 2.40 - 32.68) appears to be the main determinant of intention. Regarding the intention to seek information on STBBIs online, the explained variance of the final model is 40.17% for boys and 33.28% for girls. For boys, the main determinants of the intention to seek information on STBBIs online were cognitive attitude (OR = 6.8; CI95%: 2.13 - 21.46), affective attitude (OR = 3.6; CI95%: 1.42 - 9.14) and past behaviour (OR = 3.3; CI95%: 1.19 - 9.10). For girls, only statistical relationships were observed in the predictive models of intention to seek information about STBBIs online. In light of these results, communication strategies in Burkina Faso aiming to enhance adolescents' online information seeking about SRH should be adjusted to incorporate these determinants. While the results of this thesis support possible actions in health communication, improving adolescent SRH in Burkina Faso will require a more comprehensive and global public health approach

Objetivo: este estudo teve como objetivo avaliar as infecções por papilomavírus humano (HPV) e Chlamydia trachomatis (CT) em pacientes com artrite reumatoide (AR) pré e pós-terapia anti-TNF. Método: foram avaliadas 50 pacientes do sexo feminino com AR (preenchiam os critérios do Colégio Americano de Reumatologia) que eram elegíveis para terapia anti-TNF. Cinquenta pacientes foram incluídas no estudo de forma prospectiva. Destas, 45 pacientes foram reavaliadas após 6 meses de terapia anti-TNF. Inicialmente as 50 pacientes com AR foram comparadas com 50 controles saudáveis pareadas por idade. Foram avaliados dados demográficos, avaliação ginecológica (citologia cervical e avaliações histológicas), função sexual, parâmetros de doença e tratamento atual da AR. Os testes para detecções dos DNAs do HPV e CT nas espécimes cervicais foram realizados utilizando a captura híbrida II. Resultados: na avaliação inicial, a mediana da idade das pacientes com AR e controles foi de 49 (18-74) vs. 49 (18-74) anos, p = 1,0. Observou-se uma tendência de menor frequência de infecção por HPV nas pacientes com AR pré anti-TNF em relação aos controles (14% vs. 30%, p = 0,054). Adicionalmente, realizou-se avaliação das pacientes com AR com infecção positiva e negativa por HPV antes da terapia anti-TNF que demonstrou que o primeiro grupo apresentou maior frequência de relações sexuais (100% vs. 48%, p = 0,014), maior número de parceiros sexuais [1 (1-1) vs. 0 (0-1), p = 0,032] e maior frequência de citologia cervical anormal (43% vs. 7%, p = 0,029). A idade atual, a duração da doença, os parâmetros da doença e os tratamentos foram semelhantes em ambos os grupos (p > 0,05). Após 6 meses de terapia anti-TNF, a infecção por HPV permaneceu inalterada em cinco pacientes, enquanto que dois tornaram-se negativos e uma paciente adicional tornou-se positiva (p = 1,0). A infecção por CT foi uniformemente negativa nas pacientes com AR pré e pós-TNF, assim como nas controles. Conclusões: a infecção por HPV observada nas pacientes sexualmente ativas com AR antes da terapia anti-TNF foi leve, sem evidência de infecção por CT. A terapia anti-TNF não aumentou o risco de exacerbação e/ou progressão das infecções por HPV e CT em pacientes com AR
Objective: to evaluate human papillomavirus (HPV) and Chlamydia trachomatis (CT) infections in rheumatoid arthritis (RA) patients pre- and post-TNF blocker. Methods: fifty female RA patients (American College of Rheumatology criteria), who were eligible to anti-TNF therapy, [n = 50 at baseline (BL) and n = 45 after 6 months of treatment (6M)] and 50 agematched healthy controls were prospectively enrolled. They were assessed for demographic data, gynecologic, sexual, cervical cytology and histological evaluations, disease parameters and current treatment. HPV DNA and CT DNA testing in cervical specimens were done using Hybrid Capture II assays. Results: at BL, the median current age of RA patients and controls was 49(18-74) vs. 49(18-74) years, p = 1.0. A trend of lower frequency of HPV infection was observed in AR patients pre anti-TNF compared to controls (14% vs. 30%, p = 0.054). Further evaluation of AR patients with and without HPV infection before anti-TNF therapy showed that the former group had higher frequency of sexual intercourses (100% vs. 48%, p = 0.014), higher median number of sexual partners [1(1-1) vs. 0(0-1), p=0.032] and higher frequency of abnormal cervical cytology (43% vs. 7%, p = 0.029). Current age, disease duration, disease parameters and treatments were alike in both groups (p > 0.05). At 6M after TNF blockage, HPV infection remained unchanged in five patients, whereas two became negative and one additional patient turn out to be positive (p = 1.0). CT infection was uniformly negative in RA patients pre- and post-TNF blockage and in controls. Conclusions: anti-TNF does not seem to increase short-term risk of exacerbation and/or progression of HPV and CT infections in RA patients

Viruses can affect plant-insect interactions by altering emission of plant volatile organic compounds (VOCs). Previous work in the lab suggested that VOCs emitted by tomato (Solanum lycopersicum) plants infected with cucumber mosaic virus (CMV) were more attractive to bumblebees (Bombus terrestris) in free choice assays. I extended this work using Arabidopsis thaliana mutants with lesions in genes encoding factors in RNA silencing. In conditioning assays, I confirmed that plant VOC emission is controlled in part by the microRNA regulatory pathway. I used gas chromatography coupled to mass spectrometry and principal component analysis to confirm that CMV infection caused changes in VOC emission by tomato. VOCs collected from non-flowering mock-inoculated and CMV-infected plants were qualitatively distinct from each other. CMV-infected plants also released greater quantities of VOCs than mock-inoculated plants. CMV appears to be both ‘turning up the volume’ of plant volatile emission, whilst ‘tuning’ volatile blend composition so as to diminish levels of a repellant signal. These data are likely to explain how bumblebees can discriminate between VOCs emitted by mock-inoculated and CMV-infected plants. To determine if CMV infection of tomato plants affects plant reproductive success, I carried out a series of bumblebee pollination experiments. Bumblebees pollinate tomato by ‘buzzing’ (sonicating) the flowers, which releases pollen and enhances self-fertilization and seed production as well as pollen export. First, I established that CMV-infected tomato plants produced fruits with a lower seed yield than mock-inoculated plants. When single bumblebees were allowed to buzz-pollinate flowers in a small flying arena, the fruit that developed from buzz-pollinated flowers on virus infected plants had significantly more seeds than fruit from non-visited flowers. Subsequent experiments were performed in a large flying arena. Bumblebees consistently spent longer foraging on the mock-inoculated tomato plants but seed yield was increased by bumblebee pollination in both mock-inoculated as well as virus-infected tomato plants. However, although buzz-pollination significantly enhanced seed yield from CMV-infected plants compared to fruit from non-buzz-pollinated flowers, the yield was higher in buzz-pollinated fruits from mock-inoculated plants. Similar experiments were carried out utilizing a transgenic line of tomato that constitutively expresses the green fluorescent protein in order to estimate the level of cross-pollination from either CMV-infected plants to mock-inoculated plants or vice versa. More pollen from virus-infected plants was transferred to mock-inoculated plants than the reciprocal cross. However, some caution is needed in the interpretation of the larger scale experiments because the tomato plants were affected by a fungal infection. I investigated if the defensive plant hormone salicylic acid (SA) affects bee-perceivable VOC emission. Exogenous SA treatment renders non-flowering tomato plants more attractive to bumblebees in free choice experiments in which bees could only perceive VOCs, but bumblebees spent less time visiting SA-treated flowering tomato plants in the glasshouse (when the bumblebees were allowed unimpeded access to the flowers). Taken together, these data provide evidence that virus infection can affect host-pollinator interactions. Speculatively, CMV infection may change the fitness of susceptible plants via changes in production of pollinator-attractive VOCs and this may affect the balance of resistant or susceptible plants within the host population.

Além da deficiência física, a diminuição ou perda da sensibilidade geniturinária é um dos maiores impactos para mulheres com Lesão Medular (LM). Devido à perda da mobilidade funcional e as barreiras arquitetônicas, estas muitas vezes não tem acesso aos cuidados adequados para a saúde ginecológica. Como aproximadamente 80% das lesões da medula espinal acometem indivíduos do sexo masculino, os estudos raramente focam as necessidades e questões referentes às mulheres. Objetivo: Avaliar a prevalência de infecções genitais não virais em mulheres com deficiência física por lesão medular, comparativamente às mulheres saudáveis Método: Estudo de corte transversal, caso controle. Foram estudadas 52 mulheres com LM (grupo estudo) e 57 mulheres saudáveis (grupo controle). Todas responderam a um questionário estruturado e foram submetidas à coleta de conteúdo vaginal para pesquisa de Trichomonas vaginalis e leveduras, bacterioscopia com coloração pelo método Gram, cultura geral (meio ágar sangue), cultura para fungos (meio Sabouraud) e coleta de conteúdo endocervical para pesquisa de Chlamydia trachomatis e Neisseria gonorrhorae (reação em cadeia da polimerase) e cultura para Mycoplasmas sp (meios U9, A7). Resultados: As mulheres com lesão medular, comparativamente ao grupo controle, apresentaram maior frequência de Candida sp no exame micológico direto (p= 0,017); entretanto não foi observada diferença estatisticamente significativa na frequência de isolamento de espécies fúngicas entre os grupos. O grupo estudo apresentou maior frequência de isolamento de Escherichia coli (p= 0,002) e de Corynebacterium sp (p= 0,023) e menor frequência de Lactobacillus sp (p < 0,001) em conteúdo vaginal. Em ambos os grupos não foram encontrados casos positivos para Trichomonas vaginalis. A avaliação do escore de Nugent para diagnóstico de vaginose bacteriana demonstrou maior freqüência de flora intermediária (Nugent 4-7) no grupo estudo (p= 0,039). As pesquisas de Chlamydia trachomatis e Neisseria gonorroheae foram negativas em todas as mulheres. Com relação ao isolamento de Mycoplasmas sp, os resultados foram semelhantes em ambos os grupos. Conclusão: A menor freqüência de isolamento de Lactobacillus sp e a maior freqüência de isolamento de Corynebacterium sp e de Escherichia coli na vagina em mulheres com LM, assim como a elevada frequência de flora intermediária pelo escore de Nugent verificada nas mesmas, fortemente sugerem um desequilíbrio da microbiota vaginal, diferente de uma flora dominada por Lactobacillus sp em tais mulheres. Desde que os Lactobacillus sp são essenciais para a manutenção da flora vaginal e a inibição do crescimento de outras bactérias, sua ausência relativa em mulheres com LM pode influenciar a ocorrência de infecções do trato urogenital. Adicionalmente, a mais elevada frequência de detecção de fungos pela microscopia em mulheres com LM sugere que estas podem albergar uma maior concentração vaginal desses microorganismos do que outras mulheres
Besides their physical disability, decreased or absent genitourinary sensitivity has a huge impact in women with spinal cord injury (SCI). Due to the absence of functional mobility and the architectonic barriers these women frequently do not have access to adequate gynecological care. Since about 80% of spinal cord injuries affect men, studies have rarely focused on the needs of women with SCI. Objective: To evaluate the prevalence of non-viral genital infections in women with SCI compared to mobile women. Methods: Fifty two women with SCI (study group) and 57 mobile women (control group) were evaluated in a case-control study. All answered a structured questionnaire and were submitted to the following microbiological tests: fresh examination of vaginal secretions for Trichomonas vaginalis and yeasts, Gram stain, general culture (agar-blood medium), yeast culture (Sabouraud medium) and endocervical sampling for Chlamydia trachomatis and Neisseria gonorrhorae (polymerase chain reaction) and Mycoplasmas sp. (U9, A7 medium). Results: A higher percentage of women with SCI had Candida sp detected by direct mycological examination than did women in the control group (p= 0.017). However there were no significant differences between the two groups in the frequency of yeast-positive cultures. The study group had a higher isolation frequency from the vagina of Escherichia coli (p= 0.002) and Corynebacterium sp (p= 0.023) and a lower frequency of Lactobacillus sp (p < 0.001). In both groups, there were no cases positive for T. vaginalis, C. trachomatis or N. gonorrhoeae. The evaluation of Nugent score for bacterial vaginosis showed a higher frequency of intermediate flora (Nugent score 4-7) in the study group (p= 0.039). Related to Mycoplasma sp isolation, the results were similar in both groups. Conclusion: The lower frequency of Lactobacillus sp isolation and the higher frequency of Corynebacterium sp and Escherichia coli isolation from the vagina in women with SCI, and the higher frequence of intermediate Nugent score, strongly suggests a disequilibrium of the vaginal microbiota away from a Lactobacillus sp dominated flora in these women. Since lactobacilli are essential for maintaining vaginal health and inhibiting growth of other bacteria, their relative absence in women with SCI may influence the occurrence of urogenital tract infections in these women. The higher frequency of yeast detection by microscopy in women with SCI suggests that these women may harbor a higher vaginal yeast concentration than do other women

Porcine reproductive and respiratory syndrome virus (PRRSV) is a rapidly evolving virus that has significant economic and welfare implications for the pig industry. Vaccination strategies have proved largely ineffective in controlling PRRSV, in some cases even reverting to virulence. An increasing body of evidence suggests a host genetic basis for PRRSV resistance so there is a need to examine the role of host genetics in a biologically relevant in vitro cell culture system. However, PRRSV research is inhibited by the current scarcity of suitable in vitro culture systems. With the aim of developing a convenient in vitro model, porcine bone marrow-derived macrophages (BMDM) were evaluated as a PRRSV cell culture system. BMDM were found to be highly permissive to Type I PRRSV and amenable to genetic manipulation. BMDM proved to be excellent cells for virus production, producing significantly higher titres of PRRSV than commonly used alternative cell types. Surprisingly, PRRSV entry into BMDM was found to be independent of both the prototypic PRRSV receptors, CD163 and CD169, providing further evidence for the existence of alternate PRRSV entry mechanisms in primary cell types. To explore the genetics of pig susceptibility to PRRSV, network-based analysis of host transcriptional datasets, following PRRSV challenge, revealed important differences in co-regulated gene pathways between samples from pigs with different PRRSV-permissiveness. These pathways included genes with important, recently characterised, anti-pathogen activities. The incorporation of network-based transcriptional analysis and published genetic variation data led to the identification of a member of the guanlyate binding protein family, GBP-1, as a candidate host gene involved in controlling PRRSV replication. Overexpression of GBP-1 in BMDM revealed a significant anti-PRRSV function for this protein. Further investigation of published genetic variation in GBP-1 suggested a potential role of this gene in PRRSV tolerance. The results presented in this thesis provide evidence for an alternate PRRSV entry pathway in a biologically relevant cell type. The discovery of a highly PRRSV-infectable cell type with potential for genetic manipulation adds a useful new tool to the area of PRRSV research. The identification of GBP-1 as a novel anti-viral protein with a significant inhibitory effect on PRRSV infection, together with genetic variation in this gene, prompts further research into the genetic basis for PRRSV resistance.

The purpose of the research has been to characterize the response of naïve or virus-specific swine T lymphocytes from different lymphoid compartments to Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). Peripheral blood mononuclear cells (PBMCs), tracheobronchial lymph node (TLN) and lateral retropharyngeal lymph node (LLN) cells were labeled with PKH67 green fluorescence dye to measure cell proliferation and surface phenotypes were examined using anti-CD4, anti-CD8 or anti-CD25 monoclonal antibodies. Stimulation with Concanavalin A was also included as a positive control. Our results show that potential virus-specific T lymphocytes were found in the peripheral blood, although no cell proliferation was found in cultures of lymph node cells. We did find that the percentages of CD8+ T cells in cultures of lymph node cells from the virus-infected pig increased after in vitro stimulation with the Powell virus compared to the lymph node cells cultured in media only, suggesting that CD8+ T lymphocytes may play a role in the virus clearance and immune memory to PRRSV.

The prevalence of Hepatitis C Virus (HCV) in the US is estimated at 3.5 million with 18,153 deaths in 2016. It is the most common bloodborne infection, with a higher age-adjusted mortality rate than Hepatitis B Virus or Human Immunodeficiency Virus. Without treatment, nearly 1.1 million people will die from HCV by 2060. About 41,200 new cases of HCV were reported in 41 states in the US in 2016. The reported cases of acute HCV in 2016 is 2.3 per 100,000 in Tennessee, which is more than twice the national goal set by Healthy People 2020. This is a descriptive study to ascertain the HCV prevalence and usefulness of screening in medical outreach settings (MO) compared to indigent healthcare clinics (IHC) in northeast Tennessee. This study period was from April 2017 – February 2019. Participants (n=250), were adults, who engaged in routine, opt-out HCV testing at 4 IHC and 3 MO sites in the Tri-Cities, TN region. During the screening, demographic information- age, gender, race- were collected and the de-identified data were analyzed using Statistical Analysis System (SAS 9.3) to perform a descriptive analysis. Also, several discrete Chi-Square tests of independence between the demographic variables, screening locations, and HCV antibody prevalence was conducted. A total of 250 clients were screened for HCV. The majority of clients screened were non-Hispanic whites 228 (91.20%); females 136 (54.40%); young adults 131 (52.40%) and at IHC clinics 187 (74.80%). Screening showed HCV antibody prevalence of 14.8%. The majority of positive cases were non-Hispanic whites 36 (97.30%; P=0.1561); females 19 (51.35%; P=0.6867) and young adults 23 (62.16%; P=0.286). The prevalence at the IHC clinics and MO settings were 36 (97.30%; P=0.0006) and 1(2.70%) respectively. This analysis shows the higher yield of targeted HCV screening at IHC clinics. Focused HCV screening is critical in the era of opioid epidemic, particularly when direct-acting antiviral agents (DAAs) which offer a Sustained Virologic Response (SVR) rate of more than 90% are available. The use of case control or cohort study designs to establish causality is recommended for improving focused HCV screening.

Thesis (Ph. D.)--University of Adelaide, Dept. of Microbiology & Immunology, 1998.
Copy of author's previously published article on back end-paper. Includes bibliographical references (leaves 105-158).

Les résultats obtenus dans le cadre de cette thèse portent sur l'infection du testicule humain par le VIH. Nous avons tout d'abord montré que les celulles de Leydig isolées sont permissives à certaines souches de VIH-2 et de SIV, mais ne sont pas infectées par le VIH-1. Ensuite, nous avons adapté et caractérisé un système de culture organotypique de testicule humain. Ce modèle permet de conserver les interactions cellulaires et moléculaires de l'ensemble des types cellulaires présents au sein des explants et de préserver l'activité métabolique des cellules de Leydig. L'architecture globale des tubes séminifères et l'intégrité du tissu interstitiel sont maintenus jusqu'à 16 jours de culture. Finalement, ce modèle nous a permis d'étudier la réplication d'une souche de VIH-1 R5X4 au sein du tissu testiculaire. La production de particules virales infectieuses a été détectée dans les surnageants de cultures exposées au virus, associée à une augmentation du nombre de copies d'ADN provirales au sein des explants. En conclusion, nos résultats montrent que le testicule infecté de manière productive par le VIH in vitro, représente un réservoir potentiel pour le virus.

Zika virus (ZIKV) is a sexually transmitted viral infection most frequently transmitted by mosquitoes. The source of infectious virions in the male reproductive tract has yet to be elucidated. The goals of the studies included developing and characterizing two mouse models for reproductive transmission studies and demonstration of sexual transmission of virus via artificial insemination. The mouse strains used in the study lacked receptors to interferon molecules, key signaling proteins of the host immune response. Inflammation severity was assessed during acute disease, 5-11 days after infection using a novel histopathology grading system. ZIKV proteins and genome were initially detected in epididymal epithelial cells in males. Inflammation was first observed in the epididymis and progressed to the testicle in both AG129 and Ifnar-/- males. Infection of Ifnar-/- mice may better recapitulate Zika virus pathology in humans due to milder histopathologic lesions, the presence of histologically normal sperm in epididymal tubules, and an ability to survive the acute phase of disease. In further studies, male Ifnar-/- mice were challenged subcutaneously with ZIKV. Artificial insemination fluid derived from experimentally infected males showed positive sexual transmission at 7 days post infection (DPI) but not 35 or 70 DPI. These studies show passage of virus from epididymal flush and seminal plasma to females via insemination during acute ZIKV disease in males and provides a model for sexual transmission of ZIKV.

Porcine reproductive and respiratory syndrome virus (PRRSV) is arguably the most economically devastating pathogen affecting the global swine industry. Since the emergence of the virus in the late 1980s, vaccination strategies aimed to control the virus have not been very effective. Current commercial vaccines are generally protective against homologous or closely-related strains but ineffective at conferring heterologous protection against genetically-diverse strains of the virus. Consequently, emergence of variant and sometime more pathogenic strains of PRRSV continues in global swine herds. As such, there is a need for better understanding of the molecular mechanisms involved in the replication of the virus. In order to better understand the molecular mechanisms of host responses to PRRSV replication, we first sought to evaluate the ability of the virus to induce stress granules (SGs) during PRRSV infection. SGs are intracellular, cytoplasmic aggregates of RNA-binding proteins (RBPs) and mRNA. Formation of SGs is observed upon cellular stress and ultimately function to arrest cellular translation to promote cellular survival until the stress has been remedied. Indeed, several viruses have been shown to modulate the SG pathways to facilitate viral replication and even suppress the host's immune response. However, it is currently unknown whether PRRSV modulates the SG response. First, we used confocal microscopy and fluorescent in situ hybridization (FISH) to determine the distribution of known SG marker proteins and cellular mRNAs. Our findings revealed that PRRSV induces a potent SG response at late time points post-infection, and that SGs were closely associated with viral replication complexes (VRCs). Subsequently, we demonstrated that SGs are dispensable for viral replication, as short hairpin RNA (shRNA)-mediated knockdown of critical SG components (G3BP1 and G3BP2) did not affect viral replication. Interestingly, we found that the PRRSV-induced SGs are formed in a PERK-dependent manner. PERK is an important sensor of ER stress and activator of the unfolded protein response (UPR). Further investigation into the PERK signaling pathway revealed that PRRSV induces a significant amount of ER stress upon the cell during viral infection, and that exogenous stress significantly impaired the ability of the virus to replicate in MARC145 cells. We also showed that PRRSV potently induces all three signaling branches of the UPR, including PERK. While PERK knockdown had no effect on cell viability or viral replication, it significantly upregulated the mRNA expression of interferon-β and interferon stimulated genes (ISGs). The results from our studies suggest a critical role for PERK in regulating the host innate immune response to PRRSV infection. Only with a better understanding of the underlying molecular mechanisms of PRRSV replication will we be able to rationally design more effective vaccines against the virus.
Doctor of Philosophy
Porcine reproductive and respiratory syndrome virus (PRRSV) causes an economically-devastating disease in the global swine industry. Annually, PRRSV is estimated to cause more than $600 million in economic losses to the swine industry in the United States alone. Current commercial vaccines against the virus are not effective against the diverse field strains largely due to the extreme heterogeneity of the virus. PRRSV is also able to potently suppress several aspects of the host's immune response and therefore establish a persistent infection. The underlying mechanisms of PRRSV-mediated immune suppression are not well understood. Therefore, in this dissertation we decided to investigate the molecular mechanisms of host responses to PRRSV infection. We first investigated the ability of the virus to induce stress granules (SGs). SGs are important intracellular regulatory components that modulate many aspects of the host's cellular processes, and have even been shown to play roles in regulating viral replication and controlling immune responses to viral infection. We demonstrate that PRRSV not only induces SGs, but that the PRRSV-induced SGs are closely associated with viral replication complexes (VRCs) within infected cells. The PRRSV-induced SGs were dispensable for viral replication. PRRSV-induced SGs were previously shown to form in a PERK dependent manner. Therefore, in the second part of this dissertation research, we decided to investigate the PERK signaling pathway during PRRSV infection. PERK is an important sensor of ER stress and activator of the unfolded protein response (UPR). Our results showed that PRRSV potently induces ER stress and all three signaling branches of the UPR, including PERK. Furthermore, we revealed that PERK may play an important role in regulating the type I interferon response to PRRSV infection. The results from our studies will aid in understanding the underlying molecular mechanism of PRRSV replication which will help rationally design the next generation of more effective vaccines against this devastating swine pathogen.

Thèse de doctorat : Génétique évolutive : Paris 12 : 2005.
Version électronique uniquement consultable au sein de l'Université Paris 12 (Intranet). Titre provenant de l'écran-titre. Bibliogr. : 213 réf.

Porcine reproductive and respiratory syndrome (PRRS) is one of the most economically important diseases of swine worldwide. Since its first emergence in 1987 the PRRS virus (PRRSV) has become particularly divergent with highly pathogenic strains appearing in both Europe and Asia. However, the underlying mechanisms of PRRSV pathogenesis are still unclear. This study sets out to determine the differences in pathogenesis between subtype 1 and 3 strains of European PRRSV (PRRSV-I), and compare the immune responses mounted against these strains in both the blood and the local tissues, ie the mediastinal lymph nodes and the lung. Piglets were infected with 4 strains of PRRSV-I: Lelystad virus, 215-06 a British field strain, a vaccine strain DV and SU1-bel from Belarus. Blood was collected at various time points for viraemia to investigate viraemia and immune responses. Post-mortem examinations were performed at 3, 7 and 35 days post-infection (dpi), and cells were collected from the alveolar spaces and the lymph nodes. The subtype 3 SU1-bel strain displayed greater clinical signs and lung gross pathology scores compared with the subtype 1 strains. This difference did not appear to be caused by higher virus replication, as viraemia and viral load in broncho-alveolar lavage fluid (BALF) were lower in the SU1-bel group. Infection with SU1-bel induced an enhanced adaptive immune response with greater interferon (IFN)-γ responses and an earlier PRRSV-specific antibody response, in both blood and BALF, which correlated with gross pathology. Of particular note was the large influx of cytotoxic T cells and production of IFN-γ. On the other hand those pigs in the SU1-bel group, which had much less pathology, had the highest number of regulatory T cells and levels of the immunomodulatory cytokine Interleukin-10. The results of this study indicate that the immune response has an important role in the pathogenesis of PRRSV infection. Although these enhanced immune responses clear virus from the serum and BALF more quickly than responses seen in other strains, if these responses go unchecked, as they seem to in this case, it can have disastrous consequences for the animal. It may be possible to look at which factors are leading to this viral clearance and enhanced cellular immune response and use this data to perhaps devise a new vaccine that can monopolise on these mechanisms without causing the complications observed here.

Les termites humivores jouent un rôle primordial dans la fertilité des sols tropicaux et sont de bons candidats bio-marqueurs de la fragmentation du paysage. Dans ce travail, nous nous sommes intéressés à un termite humivore africain, originellement affilié à une seule espèce, Cubitermes subarquatus (Termitidae, Termitinae). A l'aide de marqueurs moléculiares, nous avons détecté quatre espèces cryptiques et caractérisé les systèmes reproductifs des colonies. L'étude de l'infection des colonies par la bactérie endosymbiotique Wolbachia a suggéré des modalités de transmission du symbionte particulièrement efficaces et de possibles transferts horizontaux chez les isoptères. L'identification moléculaire des souches de Wolbachia a montré qu'il existait une association stricte entre les lignées bactériennes et les espèces hôtes, suggérant plusieurs scénarios d'acquisition et posant la question de l'implication de Wolbachia dans la différenciation des espèces
Soil-feeding termites are particulary interesting models since they contribute to tropical soil fertility and could represent bio-indicators of the landscape disturbance. This work has focused on an African soil-feeding termite, originally affiliated to a single species, Cubitermes subarquatus (Termitidae, Termitinae). Using molecular markers, we detected four cryptic species and characterized the breeding systems of the colonies. A study concerning the infection by the endosymbiotic bacterium Wolbachia suggested particulary effective patterns of transmission and possible horizontal transfers of the symbiont in Isoptera. Molecular identification of Wolbochia strains revealed a strict association between the bacterium and the host species, suggesting several acquisition scenarios and asking the question of the implication of Wolbachia in the speciation process

Trypanosoma cruzi est un parasite protozoaire à multiplication intracellulaire, agent de la maladie de Chagas, infectant 16 à 18 millions de personnes en Amérique latine. Il peut être transmis de la mère infectée au fœtus dans 2 à 10 % des cas, mais ses autres effets sur la gestation ont été peu étudiés. Par ailleurs, les cytokines ont des effets sur la gestation. Certaines d’entre elles, comme l’interleukine-1, l’IL-4, l’IL-5, l’IL-10, le GM-CSF et le TGF-b2, sont bénéfiques pour la gestation, tandis que d’autres, comme l’IL-2, l’IL-12, l’IFN-g et le TNF-a ont des effets nocifs sur celle-ci. L’impact de l’infection à T. cruzi, stimulant la production de TNF-a et d’IFN-g, sur l'implantation et la croissance fœtale n’a pas été étudié.

Le but de notre travail était d’étudier les effets de l’infection aiguë à T. cruzi sur la capacité de reproduction de la souris. Nous avons ainsi évalué les effets de cette infection sur la fertilité, le développement et la viabilité des fœtus de souris et le rôle de l’IFN-g et du TNF produits au cours de l’infection sur le développement de la gestation.

Nous avons montré que l’infection aiguë à T. cruzi :i) diminue la capacité de reproduction de la souris ;ii) provoque une mortalité fœtale massive précoce (résorptions), tardive et néonatale associée à un retard de croissance intra-utérin, et ce, iii) en dehors de toute transmission congénitale du parasite.

Par ailleurs nos travaux montrent que la mortalité fœtale/néonatale est associée à une invasion parasitaire massive du placenta qui présente d’importantes lésions à type d’infiltrats inflammatoires, de nécrose ischémique, de dépôts de fibrine et de thromboses vasculaires. Nous avons noté qu’il existe une relation inverse entre la charge parasitaire des unités utéro-placentaires et la viabilité du conceptus, suggérant que ces lésions placentaires contribuent à la mortalité fœtale en limitant les échanges materno-fœtaux.

Enfin, nous avons également étudié le rôle de cytokines abortogènes comme le TNF et l’IFN-g, produites abondamment pendant l’infection aiguë de la souris par T. cruzi. Les taux sanguins maternels d’IFN-g étaient augmentés au 9ième mais pas aux 17ième et 19ième jours de gestation, alors que les taux de TNF sanguin et la production placentaire de cette cytokine augmentaient aux 17ième et 19ième jours de gestation. Afin d’évaluer le rôle de ces deux cytokines dans la mortalité fœtale, des souris ont été traitées par la pentoxifylline, pour inhiber la transcription du gène de TNF-a et diminuer la production d’IFN-g. Ces souris montraient une réduction de la mortalité fœtale à mi-gestation, associée à une diminution de la production du TNF placentaire, sans modifications des taux systémiques et sans effets sur l’IFN-g, suggérant la contribution du TNF dans la mortalité fœtale associée à l’infection aiguë par T. cruzi.

En conclusion, notre travail montre que l’infection aiguë à Trypanosoma cruzi exerce un effet particulièrement néfaste sur la capacité de reproduction et le développement de la gestation chez la souris et que les lésions placentaires liées à l’infection et la production de TNF par le placenta infecté contribuent à cet effet.

Doctorat en sciences biomédicales
info:eu-repo/semantics/nonPublished

Adolescent sexual health has been identified as a significant health and development problem facing South Africa. Limited amounts of research on sexual interactions have been undertaken, with information on adolescents’ romantic relationships being particularly scarce. Qualitative research needs to foster an understanding of the dynamics of sexual interactions in specific settings, and with emphasis in the past on cognitive health psychology models, very little is thus known about how adolescents negotiate and make sense of their sexual experiences. This highlights the need to investigate the complexities of human sexuality in a contextual manner. In response, this study explores the lived experiences of four young black women as they negotiate their agency and sexuality in a local context. By way of in-depth qualitative interviews, which were analysed for recurrent themes using interpretative phenomenological analysis, this project examines the participants’ experiences regarding sex, relationships, communication, sexual health care, as well as HIV and pregnancy prevention. The results reveal that communication about sexuality in the participants’ homes was limited if not absent altogether. When seeking sexual health care, they found clinic nurses to be judgemental and rude. Regarding sexuality and HIV education, the participants stressed the need for outside educators to teach in more practical ways to increase efficacy. In their dating relationships, most participants revealed their boyfriends had a great deal of influence over their sexual initiation. Unwanted pregnancy surfaced as a greater fear than HIV in their accounts due to pressure to finish their education and attain well-paying jobs in the future. The participants felt unable to stop their boyfriends’ infidelity and had limited agency when facing sexual demands. Their accounts revealed that they negotiate their agency in an atmosphere of coercion and the threat of rape. However, areas of agency included their consistent condom use even when facing pressure to have unprotected sex, and their active accessing of sexual health services for hormonal contraception. These insights serve to better inform sexual and reproductive health education and intervention programmes for young women. Moreover, educators, researchers and programme developers alike may gain useful insights from the personalised accounts derived from this study.

Porcine reproductive and respiratory syndrome virus (PRRSV) is arguably the most economically-important swine pathogen. As the emergences of novel virulent strains of PRRSV continue to occur worldwide, rapid vaccine development is the key for effective control of ongoing PRRSV outbreaks. With the availability of the PRRSV reverse genetics systems, rapid vaccine development against PRRSV through the manipulation of the reverse genetics becomes feasible. To facilitate the vaccine development effort and study of PRRSV genes, we first established a DNA-launched infectious clone of the passage 14 PRRSV strain VR2385, pIR-VR2385-CA, and identified a spontaneous 435-bp deletion in the nsp2 gene. To characterize the biological and pathological significance of this nsp2 deletion, we restored deleted nsp2 sequence back to pIR-VR2385-CA and constructed another clone pIR-VR2385-R. VR2385-CA and VR2385-R were successfully rescued in vitro. The results from this study indicates that the spontaneous nsp2 deletion plays a role for enhanced PRRSV replication in vitro but has no significant effect on the pathogenicity of the virus. With the availability of the DNA-launched infectious clone of PRRSV, we successfully applied the molecular breeding approach to rapidly attenuate PRRSV. The GP5 envelope genes of 7 genetically divergent PRRSV strains and the GP5-M genes of 6 different PRRSV strains were molecularly bred. DS722 with shuffled GP5 genes and DS5M3 with shuffled GP5-M genes, were successfully rescued in vitro and shown to be attenuated both in vitro and in vivo. Furthermore, DS722, but not DS5M3, still elicit similar protection against PRRSV challenge as its parental virus. This study reveals a unique approach through DNA shuffling of viral envelope genes to attenuate a positive-strand RNA virus. We subsequently utilized the novel synthetic attenuated virus engineering (SAVE) approach to attenuate PRRSV. The GP5 and nsp9 genes of PRRSV were codon-pair deoptimized with the aid of a computer algorithm. SAVE5 and SAVE9 with deoptimized GP5 gene and SAVE9 with deoptimized nsp9 gene, were successfully rescued and shown to be attenuated in vitro. An in vivo pathogenicity study indicated the attenuation of SAVE5 virus in vivo. The results have important implications for rapid vaccine development against PRRSV and other important viruses.
Ph. D.

Les infections à Papillomavirus Humain (HPV) sont des infections sexuellement transmissibles très fréquentes. La persistance de ces infections est un facteur causal du cancer du col de l'utérus et est aussi à l'origine d'autres cancers de la zone ano-génitale et de verrues génitales chez les femmes et chez les hommes. Depuis l'introduction de deux vaccins bivalent et quadrivalent permettant de prévenir certains types d'HPV, de nombreux modèles mathématiques ont été développés afin d'estimer l'impact potentiel de différentes stratégies de vaccination. L'objectif de ce travail de thèse a été d'estimer l'impact potentiel de la vaccination en France sur l'incidence de certains cancers liés à l'HPV, notamment le cancer du col de l'utérus et le cancer anal chez les femmes françaises ; ainsi que sur la prévalence des infections à HPV 6/11/16/18. Différents modèles dynamiques de type déterministe ont été développés. Ils sont représentés par des systèmes d'équations différentielles ordinaires. Une étude théorique du comportement asymptotique d'un premier modèle comportant peu de strates a été réalisée. Le nombre de reproduction de base R0 et le nombre de reproduction avec vaccination Rv ont été estimés. Des modèles plus complexes ont intégré une structure d'âge et de comportement sexuel. Les modélisations réalisées permettent de conclure à l'impact important de la vaccination sur la prévalence des infections à HPV et sur l'incidence des cancers du col de l'utérus et de la zone anale chez les femmes françaises dans un délai de quelques décennies, si l'on prend en compte les taux de vaccination observés en France au début de la campagne de vaccination