Data management in resource-limited settings can be a mountainous problem if not approached with a thorough understanding of those limitations and a mindset prepared for rapid changes in the environment. Data management becomes even more challenging at multiple points of entry, where there are many interwoven parts working together in order to get a potential traveler from his/her first steps into an airport area to boarding a plane, all while ensuring that the traveler has been thoroughly screened for any signs or symptoms of a possible Ebola virus disease infection. This capstone describes the history of the International Health Regulations’ effects on control of disease spread and importation at points of entry, the Do Not Board/Lookout List’s role in disease control in the United States, and the CDC’s International Assistance Team’s unique task in creating and implementing country-specific databases to meet the needs of Ebola-affected countries. The most critical data management need at these countries’ points of entry is specifically to prevent the exportation of Ebola virus disease in order to keep each country’s airspace open and allow goods, personnel and services to continue to be imported into these countries during this sustained Ebola outbreak.

Philosophiae Doctor - PhD / Introduction: This study was conducted because of a gap in information on the factors influencing the health promoting schools (HPS) implementation process in South Africa (SA) specifically and in secondary schools globally. The aim of this context- sensitive, practice-based study was to explore and understand the complexity of the factors that influenced the implementation process of HPS in three secondary schools in a resource-limited setting in Cape Town, SA. This research drew on a five year project that initiated the implementation of HPS in these schools. Methodology: An exploratory qualitative study was used, adopting a multiple case study design. The sample included two principals, ten teachers and 30 students involved in HPS implementation at their schools, and the three school facilitators, who served as mentors to the schools. The data collection methods included: individual interviews, focus group discussions, documentary review, secondary data and observations. A conceptual framework was developed drawing on the settings approach and various implementation frameworks and was used to analyse the findings. Thematic analysis was employed and the data for each case were analysed separately first before undertaking cross case analysis. Findings: A combination of several internal and external factors influenced the ability of the schools to implement and integrate HPS as a whole school approach. A key factor was the degree of understanding of the HPS concept by all key actors and where there was lucid understanding, there was better integration. Significant school factors included the schools’ readiness for change; a culture of collaboration and cooperation; existing school structures, practices and workload; the leadership style and management role of the principals; the role and influence of HPS champion teachers; and the role that students played. The major external factors included the role of the education district; the role of project team as external catalysts for change; and the community context. The main achievements in all schools were discrete activities, including co-curricular activities rather than changes to routine school functions. This highlighted the difficulty in implementing HPS as a whole school approach, a challenge typical of all health promoting settings. Conclusion: The findings illustrate the challenge of achieving full integration of HPS, although the influencing factors, and hence level of integration varied mainly according to context. This highlights the complexity of the different factors and their impact. The study demonstrates the paradox of HPS implementation. In that, despite the recognition of the value of HPS, the challenges to address the complexity of factors that would have brought about change through a whole school approach were too great. It was too difficult to change the status quo from what was routinely done to a more radical way of working due to the conservatism of traditional ways of working and extent of adjustment that it would have resulted. It was therefore only possible to put simple, discrete, strategies in place and that was not too resource intensive. The study concluded that this does not imply that HPS should not be attempted, particularly where there are adverse conditions that would benefit from HPS. Starting with marginal changes, it can be effective in increasing the schools’ readiness for change, building on the achievements both in activities and structures, and the resultant commitment by those involved. Once they experience these changes it will more likely enable schools to incrementally attempt more complex changes. The key recommendations for within the school include: building the understanding and capacity of relevant actors to actively support the implementation of HPS; building the capacity of the principal to create an environment which is conducive to change; and providing support for the HPS champions and students. Recommendations for those external to the school include: support from external catalysts who can provide expertise and mentorship; support from the education district, especially in terms of policies on integration, resources, and raising the profile of HPS; and better collaboration between the education and health sectors. Although most of the literature on HPS implementation identifies similar issues to those found in this study, the complexity has not, to date, been sufficiently described. The contribution of this study, therefore, is to take the debate on the complexity of the factors influencing HPS implementation forward.

Les tests moléculaires sont fréquemment demandés pour le diagnostic et le suivi des maladies infectieuses dans les pays développés. Cependant, sa disponibilité reste limitée dans les pays à ressources limitées dû à des contraintes de coûts, des technologies et des ressources humaines. Dans les régions éloignées, un accès limité aux installations de laboratoire constitue également un problème majeur. Le développement de méthodes de PCR sur plateformes ouvertes dans des laboratoires de référence tels que le Centre MURAZ au Burkina-Faso et l'utilisation d’échantillons de sang total capillaires sur DBS peuvent faciliter l'accès aux tests moléculaires.Selon la directive de l'OMS, la quantification de l'ARN du VIH à l'aide de DBS peut être une alternative dans les contextes d’accès difficile au laboratoire. Une préoccupation majeure est la spécificité sous-optimale de l’utilisation des DBS en raison de l'interférence de l'ADN du VIH archivé dans des cellules infectées sur la charge virale ARN du VIH. Dans une première étude, nous avons déterminé le niveau d'ADN du VIH-1 qui entravait la fiabilité de la quantification de l'ARN du VIH-1 sur des DBS. Une détection d'ARN du VIH-1 faussement positif (22/62, 35%) a été associée à des niveaux élevés d'ADN de VIH-1. Nos résultats indiquent que la spécificité des tests d'ARN du VIH-1 sur les DBS devrait être évaluée suivant les protocoles du fabricant sur les échantillons avec des niveaux d'ADN de VIH-1 de ≥1 000 copies / 106 cellules mononuclées du sang périphérique.Outre les infections fréquemment diagnostiquées, il est urgent d'intensifier la recherche d’infections négligées comme la leptospirose. Dans une seconde étude, nous avons exploré la leptospirose par des tests sérologiques et moléculaires comme cause négligée de maladie chez les patients atteints d’ictère fébrile au Burkina Faso. Les résultats ont montré pour la première fois que la leptospirose est une cause insoupçonnée de maladie fébrile aiguë dans ce pays semi-aride.Dans la dernière partie du doctorat, nous avons développé un test de PCR multiplex pour le diagnostic de la méningite à herpès simplex virus (HSV) et à Mycobacterium tuberculosis (MTB) chez des patients suspects de méningite aseptique. Cette qPCR qui a permis de tester dans un seul essai HSV 1/2 et MTB était très spécifique, sensible et reproductible. La concentration d'ADN la plus faible donnant 100% de signal de détection a été estimée à 2,12 copies / μl pour HSV1, 1,76 pour HSV2 et 2,15 copies / μl pour MTB. Parmi les 202 échantillons de LCR inclus dans cette étude, 5 (2,46%) étaient positifs: 2 (0,99%) pour HSV et 3 (1,47%) pour MTB. Ce test peut être particulièrement utile dans les cas de méningite / encéphalite avec un faible nombre de globules blancs dans le CSF.Notre projet a montré l'importance de la mise en œuvre de nouvelles méthodes moléculaires pour fournir des données préliminaires sur le fardeau des maladies infectieuses, y compris la leptospirose, la tuberculose et la méningite à HSV au Burkina Faso. Le DBS est un spécimen alternatif qui facilite l'accès aux tests moléculaires mais nécessite des études de validation. Les approches syndromiques doivent être testées et mises en œuvre dans les pays à ressources limitées en se basant sur l'expertise locale et la mise en œuvre de méthodes moléculaires dans les laboratoires de référence. / Molecular assays are frequently requested for the diagnosis and monitoring of infectious diseases. While nucleic acid testing is the standard of care in developed countries, its availability remains limited and constrained by cost, technologies, and human resources in many settings, including West Africa. In remote areas, limited access to laboratory facilities is also a main issue. The development of PCR methods on open polyvalent platform in reference laboratories such as the Centre Muraz in Burkina-Faso and the use of capillary whole blood collected on DBS specimens can facilitate access to nucleic acid testing.According to WHO guideline HIV-RNA quantification using DBS can be considered in settings where there is a lack of access to sites or nearby laboratory facilities for nucleic acid test. A major concern is the suboptimal lower specificity of DBS due to the interference of HIV-DNA copies archived in infected cells with HIV-RNA copies. In the first study we determined the HIV-1 DNA level that interfered with the reliability of HIV-1 RNA quantification on DBS specimens used for therapeutic monitoring (1). False-positive HIV RNA detection (22/62, 35%) was associated with high HIV-1 DNA levels. Our results indicate that the specificity of HIV-1 RNA assays on DBS should be evaluated following manufacturer protocols on samples with HIV-1 DNA levels of ≥1,000 copies/106 peripheral blood mononuclear cells.Beside infections frequently tested by nucleic acid tests there is an urgent need to scale up assay for neglected infection such leptospirosis. In the second study we explored leptospirosis by serological and molecular testing as a neglected cause of disease among patients with febrile icteric illness in Burkina Faso. The results showed for the first time that leptospirosis is an unsuspected cause of acute febrile illness in this semi-arid country.In the last part of the PhD, we developed a multiplex PCR assay for the diagnosis of tuberculosis and Herpes Simplex (HSV) meningitis among patients with suspected aseptic meningitis. This qPCR which allowed to test in a single run HSV 1/2 and M. tuberculosis was highly specific, sensitive and reproducible. The lowest DNA concentration giving 100% detection signal was estimated at 2.12 copies/µl for HSV1, 1.76 for HSV2 and 2.15 copies/µl for M. tuberculosis. Of the 202 CSF specimens included in this study, 5 (2.46%) were tested positive: 2 (0.99%) for HSV and 3 (1.47%) for M. tuberculosis. This assay may be especially useful in cases of meningitis/encephalitis with a low number of white blood cells count in the CSF.Our project stresses the importance of the implementation of news molecular methods to provide preliminary data about the burden of infectious diseases including leptospirosis, tuberculosis and HSV meningitis in Burkina Faso. DBS is an alternative specimen that facilitates access to nucleic acid tests but requires validation studies. Syndromic approach need to be tested and implemented in West Africa and should be based on local expertise and implementation of molecular methods in reference laboratories.

Objective: The objective of this retrospective cohort study is to assess whether demographic and anthropometric parameters, laboratory tests, co-morbidity, co-infection, treatment regimen, IRIS and adherence predict response to HAART as measured by CD4 count, weight gain and functional status in a cohort of patients in Roma, the Kingdom of Lesotho. Method: Data were collected from a computerised database of the Antiretroviral Centre of the hospital. A cohort of 300 subjects was identified from hospital records from January 2007. Each of these subjects was followed up over a period of 12 months with data obtained for at least two visits within the 12-month span. Data were obtained on weight and CD4 at baseline, three months and also at six and 12 months, and data for haemoglobin were obtained only at 12 months. Variables that may be potential confounders were identified and univariate and multivariate logistic regression analyses were carried out to establish differences independent of confounding factors for the combined endpoints, as well as for each endpoint separately. Results: Three-hundred patient records were analysed. Approximately 70% of the patients had a CD4 increase of at least 150 cells over baseline values at the end of the review period and in 52.3% of the patients an increase in weight of 10% over baseline measurements was seen. Seventy-nine patients (26.3%) had a haemoglobin level of at least 14g/dL at 12 months, regardless of baseline values or gender. The inclusion of Zidovudine (AZT) in treatment regimens was found in 73% of the patients and in multivariate analysis AZT was associated with not having anaemia at the end of the review period. However there was a slight reduction in haemoglobin level in the first two to three months of therapy in comparison with both Stavudine (d4T) and Tenofovir (TDF) but not significant enough to result in clinical anaemia. Baseline CD4 values were similar for all treatments options but dissimilar in other outcome variables and continued to vary significantly throughout the review period. The outcomes of multivariate analyses suggest that the male gender appears to have better response to HAART as seen in each of the multivariate models. The most important determinant of haemoglobin response was baseline haemoglobin values. In the haemoglobin-associated multivariate model, HAART is associated with an increase in haemoglobin over baseline values. A history of TB prior to HAART was a major factor in weight response and it is thought to be as a result of IRIS, which is the unmasking of latent infections as the immune system reconstitutes. CD4 values have no direct influence on weight however, but an increase in weight was observed in all therapy groups. Conclusion: Clinical and immunological parameters can be used to monitor response to HAART and predict treatment outcomes. These parameters can be organised into monitoring tools that will be useful in resource-limited areas. This study suggests that AZT-containing regimens appear not to result in anaemia and that symptomatic anaemia might need additional investigation. Treatment with TDF appeared to have shown the best possible response pattern more but patients on TDF therapy will have to be included in the study to justify this observation. / Dissertation (MSc)--University of Pretoria, 2012. / Clinical Epidemiology / unrestricted

No description available.

<p><font face="Times New Roman"> <p align="left"><font face="Times New Roman"><b><font face="Times New Roman">Aim</font><font face="Times New Roman">: To obtain baseline data on adherence levels and the major determinants of adherence among patients on HAART at Rundu Hospital, Namibia.</font></b></font></p> </font></p>

<p><font face="Times New Roman"> <p align="left"><font face="Times New Roman"><b><font face="Times New Roman">Aim</font><font face="Times New Roman">: To obtain baseline data on adherence levels and the major determinants of adherence among patients on HAART at Rundu Hospital, Namibia.</font></b></font></p> </font></p>

Magister Public Health - MPH / Aim: To obtain baseline data on adherence levels and the major determinants of adherence among patients on HAART at Rundu Hospital, Namibia. Results: Seventy-eight percent of the 97 participants included in the study were female, resulting in a female to male ratio of 4 :1. The mean age of the participants was 36.7 (SD: 9.00) years with 80% of the participants being in the 20-44 age group. The mean duration on ART treatment was 20 (SD: 10.3) months with 76% of the participants being on ART for 24 or less months. The average adherence rate reported by mean composite of the three measures was 95.1%, while the proportion of patients who achieved adherence levels of 95% and above was 64%. The main barriers to adherence to HAART reported by participants were forgetfulness (28%), lack of food (13%) and being away from the pills (11%): facilitators reported included counselling (19%) and treatment supporters (11%). Having knowledge of the consequences of failing to take HAART as prescribed was significantly associated with adherence (p = 0.03), as was being female (p = 0.04) while living further than 6 km from the hospital was significantly associated with non adherence (p = 0.018).

Depuis 1994, l’ANRS mène en tant que promoteur des études cliniques dans les pays à ressources limitées. Ces études sur le Sida et les hépatites virales sont principalement menées dans les huit sites de l’agence en Afrique Subsaharienne, au Moyen Orient, en Asie du Sud-Est et en Amérique Latine. Les chercheurs dans les pays à ressources limitées font face à deux problématiques majeures : (i) les règles des Bonnes Pratiques Cliniques (BPC) n’intègrent pas leurs particularités fonctionnelles et culturelles ; et (ii) aucun outil n’existe dans la littérature pour évaluer l’adhésion des études cliniques à ces règles. Les objectifs de cette thèse sont premièrement d’identifier les particularités des études cliniques menées dans les pays à ressources limitées et développer par consensus des Indicateurs de Qualité (IQ) adaptés à leur contexte. Ensuite, d’appliquer ces IQ à des études cliniques menées dans les sites ANRS pour évaluer leur faisabilité et leur pertinence. Les IQ proposés ont couvert essentiellement huit processus : (i) rédaction du protocole et demande des autorisations ; (ii) inclusion et suivi des participants ; (iii) monitorage des sites ; (iv) gestion du médicament ; (v) examens biologiques ; (vi) gestion de l’archivage ; (vii) gestion de la base informatique ; (viii) clôture des sites cliniques. Le recueil des données a été réalisé dans neuf essais cliniques (2137 patients inclus) dans les six pays partenaires. Parmi les 58 IQ prédéfinis, 45 IQ ont été faisables et pertinents. Cette démarche originale a permis la mobilisation des acteurs des recherches financées par l’ANRS dans les pays à ressources limitées autour d’une véritable démarche qualité. Les résultats des IQ recueillis dans le cadre de ce programme ont montré que pour les notions essentielles les essais de l'ANRS sont conformes aux références BPC, ICH, et CIOMS. Le maintien et le suivi de cette démarche permettra à l’ANRS de veiller en permanence sur la qualité et la fiabilité des données des études et garantira la transparence des procédures et la sécurité des participants. / Since 1994, the ANRS has funded research sites in resource-limited countries (RLCs). Studies on AIDS and viral hepatitis are mainly conducted in the eight ANRS sites in Sub-Saharan Africa, the Middle East, Southeast Asia and Latin America. Researchers in RLCs face two major problems: (i) little guidance exists on how recommendations and regulations should be interpreted and applied in non-investigational new product trials and in the context of RLCs and (ii) in the literature there is not a standard tool assessing adherence of clinical studies to these guidelines. Objects of this thesis were firstly to identify specific considerations of clinical studies in RLCs and to develop by consensus methods Quality Indicators (QIs) adapted to their context. Then evaluate QIs feasibility and relevance through data collection in ANRS clinical trials. The proposed QIs covered eight main processes: (i) Protocol conception and seeking authorizations, (ii) participant enrollment and follow up, (iii) site monitoring, (iv) drug management, (v) biological investigations; (vi) records management, (vii) data management (viii) site close out. Data collection was carried out in nine trials (2137 patients) in the six participating sites. Of the 58 proposed IQ, 45 were feasible. This innovative program allowed ANRS sites located in resource-limited countries to share their GCP implementation experiences in order to build a list of relevant indicators for clinical trials. QI were able to assess the quality of all major processes of clinical trials and showed that major ethical and GCP requirements were respected in all nine ANRS trials. This permanent monitoring can be used to enable continuous practice improvement, ensure participants’ safety transparent procedures and guarantee data quality and reliability in all studies funded in resource-limited countries.

<p>Eligibility for antiretroviral therapy (ART) in HIV-infected patients is defined either by a cluster of differentiation antigen 4 (CD4) count of less than 200cells/mm3 or clinical diagnosis of WHO stage III and IV. Therefore, the decision to start ART becomes difficult when CD4 cell count is not available. With limited laboratory infrastructure, the decision to start ART is usually made based on clinical symptoms leading to late commencement of ART. This calls for alternative criteria to see if nail discoloration (ND) correlates with low CD4 count among untreated HIV infected patients. This will serve as a complementary screening tool for identifying asymptomatic ARV naive HIV patients with a CD4 cell count of less than 200cells/mm3 which signifies&nbsp / severe immunosuppression. Study Design and Setting: This was a quantitative cross-sectional descriptive and analytical study involving adult ART na&iuml / ve HIV infected patients in WHO stage I and II. Systematic sampling was used to select the participants from all adult ART na&iuml / ve HIV infected patients attending APIN clinic, located at the Jos University Teaching Hospital (JUTH), Jos, Nigeria. Data Collection: Face-to-face interviews, physical examination and relevant laboratory investigations with selected participants were conducted using a questionnaire guide. Questions on socio-demographic characteristics, clinical data, general physical examinations including finger nail examination and photographing with subsequent laboratory investigations including CD4 count and western blot were employed. Data Analysis: Variables were categorized and data analyzed using descriptive statistics including the frequency, percentage frequency / mean and standard deviation of continuous variables. Association between CD4 count of &le / 200cells/mm3 and ND was tested using the chisquare test with an alpha level of 0.05. Prevalence of ND, sensitivity, specificity, positive predictive and negative predictive values and accuracy of the screening test of ND was calculated. Results: 394 patients had their fingernails photographed and assessed. It was shown that distal banded and grey nails were the common types of ND seen with a prevalence of 38%. There was an association between CD4 count &le / 200cells/mm3 and ND (p&lt / 0.0001). CD4 count &le / 200cells/mm3 was a risk factor for developing ND (RR=2.3[1.8-3.6]). The association has a sensitivity of 78%, specificity of 55%, positive predictive value of 50%, and negative predictive value of 80% and accuracy of test 63%. Conclusion: With a significant association (p&lt / 0.0001) and a sensitivity of 78%, ND can be a useful clinical indicator of immune dysfunction mediated by HIV among patients in WHO stage I or II. ND can either be a clinical sign or a symptom in HIV patients with a CD4 of &le / 200cells/mm3 as seen in the study as the specificity and sensitivity of ND compared favourably with other WHO stage III diagnosis. Recommendations: Nail discoloration should complement CD4 count as an additional staging sign to help identify patients likely to benefit from ART especially in resource-limited settings. Finally, all patients with grey or distal banded should be on co-trimoxaxole prophylaxis in line with WHO /national guideline on the use of co-trimoxaxole for all HIV positive patients with a CD4 cell count of &le / 350cells/mm3.</p>