Thesis (Ed. D.)--Illinois State University, 2002. / Title from title page screen, viewed February 16, 2006. Dissertation Committee: Dent Rhodes (chair), Donna Breault, Sheryl Samuelson, Cathy Toll. Includes bibliographical references (leaves 172-178) and abstract. Also available in print.

Thesis (B.A.)--Haverford College, Dept. of Economics, 2006 / Includes bibliographical references.

Thesis (Ph. D.)--Georgia State University, 2005. / Lisa Armistead, committee chair; Leslie Jackson, Sarah Cook, Page Anderson, committee members. Electronic text (145 p. : ill.) : digital, PDF file. Title from title screen. Description based on contents viewed July 26, 2007. Includes bibliographical references (p. 99-116).

The joint United Nations programme on HIV/AIDS (UNAIDS) in collaboration with the World health Organization (WHO) published a report stating that, 42 million people are living with Human Immunodeficiency Virus (HIV) globally, where 20 million people had already died and where HIV, the virus that causes Acquired Immune Deficiency Syndrome continued to spread in all countries (Pratt, 2003). In South Africa it is estimated that a total number of 5.6 million individuals have acquired HIV infection by the end of 2003 (Department of Health, 2004). Highly active antiretroviral treatment (HAART) is presently the treatment of choice for people with HIV/AIDS. These drug cocktails of protease inhibitors and nucleosides led to the first real medical progress in the treatment of the epidemic. Although most people with HIV/AIDS are encouraged by the results of using the cocktail of Antiretroviral drugs (ARV’s), a recent study published indicated that 27% of people who are HIV positive have an infection that is resistant to all three classes of HIV drugs presently available (Voelker, 2000). This evidence show that there is a need for Alternative and Complementary Therapies to treat a significant number of people living with HIV infection. The aim of this study was to determine, by means of a questionnaire survey the perceived effect of Complementary Immune Boosters in HIV/AIDS patients in Johannesburg, Gauteng. This study also determined the knowledge people have of HIV/AIDS and how patients knew about the availability of Complementary Immune Boosters. Age, gender, marital status and employment status of patients were also determined. This study involved acquiring questionnaire survey responses from 200 participants in Johannesburg, Gauteng. Participants were recruited from twenty health shops and pharmacies that purchase Complementary Immune Boosters. A motivating letter (Appendix A) was hand delivered to health shops and pharmacies by the researcher prior to the completion of the questionnaire (Appendix B) to notify the pharmacist or health shop attendant about the research. Responses were recorded and correlated and analysed using qualitative and quantitative methods, including descriptive statistics. The results of this study provide a database estimating how effective Complementary Immune Boosters are on HIV/AIDS patients and reasons why HIV/AIDS patients choose to utilize Complementary Immune Boosters to boost their immune system or to relieve some of their symptoms. Of the 200 respondents only 40% said they are HIV positive, 22.4% said they are not and 37.6% said they do not know if they are HIV positive. The data showed that the percentages of respondents are almost equal with males (51.0%) and females 49.0%. In addition, the majority of respondents are blacks with 81.8%, the second group are whites 8.6%, and coloured 7.1% and Asians are only 2.5%. Cellfood (26.8%) was the most used product by respondents, followed by Hypoxis Hemenocallidea (African potato) 17.7%. The remaining 55,5% was shared by other Immune Boosters. Most respondents said they consume Complementary Immune Boosters to boost their immune system. Data showed that only 1.5% of respondents were advised by their medical practitioners to use Complementary Immune Boosters. With the study done on attitudes of medical practitioners regarding Complementary medicine in South Africa, 70% of medical practitioners felt that Complementary and Alternative Medicine should play an active role in the health care system in South Africa (Selli, 2003). The results of this study are expected to initiate further, much needed research in the area of HIV/AIDS and Complementary and Alternative Medicine. / Dr. M.R.A Moiloa Dr. S. Koopedi

In vitro infection is a fundamental part of HIV research. A successful detectable infection forms the basis for most experimentation on drug design or vaccine development. Deviation from this infection gives insight into whether a particular treatment regimen may be effective or not. For example, neutralization assay used in vaccine studies to evaluate induction of neutralizing antibodies requires in vitro infection of cells and measuring the ability of serum antibodies to reduce or prevent an infection. Drug screening also uses the ability to limit infection as the proof of a successful interference with virus production. Infecting peripheral blood mononuclear cells (PBMCs) is a very important tool for generating viral stocks (cell free or PBMC-associated) which can be used to infect other cells. Generating these stocks is costly and limiting the use of large volumes of cellfree viral stocks as well as increasing virus yield makes research more cost effective. Thus, studying factors that increase in vitro infection can help us limit virus stock use and provide information on how one can in future gain higher yields from co-culture. This work focused on subtype C since it is the strain that infects most people worldwide and is most abundant in South Africa. Objectives: We wanted to evaluate methods used for enhancement of in vitro infection and possibly develop an in vitro infection protocol for consistent and persistent infection. DNA PCR is not valued as a means of detecting in vitro HIV-1 infections and measuring the secretion of p24 by specialisedELISA is preferred. We therefore wanted to evaluate whether the enhancement of in vitro infection would lead to a better detection of infection in vitro by standard DNA PCR or Real-time(RT)-PCR. Since NF-êâ (a host transcription factor) was identified as playing an essential role in the production of virus the next goal was to evaluate the effect known enhancers of this transcription factor would have on detection of in vitro infection because of a potential increase in virus production. Hypothesis: Spinoculation and NF-êâ enhancement by inducting stimulus gives a higher thus more consistent infection in vitro that can be detected using standard molecular techniques. Methods: Spinoculation and polybrene addition was applied to PM1, CEM.NKR-CCR5 or PBMC cultures to boost infection. Further increase in virus production was attempted using three NF-êâ enhancers. DNA PCR, RT-PCR and p24 ELISA was applied to detect enhancement of infection using the viral strain Du-151. Results: Spinoculation (1200 x g for 3 hours) was superior to polybrene as an enhancer of in vitro infection and this was demonstrated with p24-ELISA, DNA PCR and Real-time PCR. NF-êâ enhancement through UV-C irradiation enhanced viral production in the macrophage/T-cell tropic cell line PM1 (p<0.05) and was superior to H2O2 and LiCl. LiCl had a more pronounced effect in the case of PBMCs. (p<0.05) A viral concentration of 500 TCID50 was sufficiently DNA PCR detectable following 7 day incubation provided that spinoculation and UV-C irradiation was also applied. PM1 was persistently infected in vitro and is in our opinion better suited for experimentation due to the fact that it does not show the degree of cytotoxicity of CEM.NKR-CCR5. This cell line also is known to produce infectious virus that sustain the infection. Conclusion: Detectable PCR results were obtained with 500 TCID50 and the use of enhancing factors. One of these enhancing factors is spinoculation. Spinoculation is a better technique to use to enhance cell virus contact and lacks the toxicity of polybrene. NF-êâ enhancement by UV-C has the best effect on virus production in PM1 where LiCl was found to be better suited for PBMC. DNA PCR can be used to successfully detect infection when enhancing techniques are applied. / Dr. Debra Meyer

M.Tech.

M.Tech.

Includes bibliographical references / Background: Tuberculosis (TB) control depends on interrupting transmission through rapid diagnosis and treatment initiation of infectious TB cases. With increasing delay in the diagnosis and treatment of pulmonary TB, disease is likely to progress, leading to progressive lung cavitation and increased sputum bacillary load, likely increasing TB transmission. This study investigated the effect of treatment delay in adult TB patients on the risk of TB infection and disease in child household contacts. Methodology: Secondary analysis was performed using data from a community-based household contact investigation study. Cross-sectional analysis was conducted of baseline data collected at enrolment. Children aged three months to fifteen years with documented household exposure to an adult with TB were enrolled between December 2007 and June 2012. These children were screened for TB infection (Mantoux tuberculin skin test [TST] and two interferon-gamma release assays [IGRA]) and disease. Total treatment delay was measured in adult TB source cases as the time from cough onset until treatment initiation, with those reporting no cough serving as the reference category. Logistic regression models were used to evaluate the effect of total treatment delay in adults on the risk of TB infection in child household contacts, with TB disease evaluated as a secondary endpoint. Results In total 671 children were enrolled as household contacts of 290 adult TB source cases. In multivariate analysis, the odds of TST positivity increased with cough duration ≥4 weeks prior to TB treatment initiation (odds ratio (OR) = 1.77 [95% CI 1.02-3.09] for cough <4 weeks; OR = 2.74 [95% confidence interval ( CI ) = 1.39-5.40] for cough 4-12 weeks; OR = 2.39 [95% CI = 1.19-4.82] for cough >12 weeks, compared to non-coughing adult TB patients), child's age ≥5 years (OR = 4.51, [95% CI = 2.60-7.83]), sharing the same bedroom (OR = 2.17, [95% CI = 1.43-3.31]), more than one household TB contact (OR = 2.70, [95% CI = 1.35- 2 5.42]) and with household tobacco smoke exposure (OR = 2.10, [95% CI = 1.22-3.61]). Adult TB source case HIV status did not modify the association between cough duration and risk of infection in children. Results of analyses of TB infection indicated by IGRA positivity were consistent with TST results. Prevalent TB disease in child contacts was associated with source case sputum smear and culture positivity, additional household TB contacts and decreasing age of the child. Conclusions: Delays of longer than four weeks from cough onset until TB treatment initiation were associated with increased risk of TB infection in child household contacts. These findings confirm the importance of reducing delays in TB diagnosis and treatment in adults to reduce transmission, ideally to less than four weeks. Although HIV co -infected TB patients are often considered less infectious, delayed treatment initiation remained associated with TB transmission, even amongst HIV co-infected adults with TB. In addition to the traditional risk factors for developing TB disease after infection, source case exposure factors also increased the risk of exposed children developing TB disease.

Background: HIV transmission is greatly reduced when antiretroviral treatment (ART) suppresses an infected person’s HIV viral load. It is unclear, however, whether the contextual risk of incident HIV is optimally reduced by widespread individual-level suppression of HIV viral load alone or in combination with other HIV prevention services. HIV service coverage and community norms can influence risk in small area geographies; and contextual factors, like gender inequality and stigma, may foster environments conducive to HIV transmission. Yet, the relationship between places with high HIV levels and the clustering of area risk factors is unknown. The goal of this dissertation is to learn if and how a geographically focused combination implementation strategy could reduce population-level HIV risk. Analyses explored whether small area risk profiles explain area differences in HIV. The guiding hypothesis is that in high HIV prevalence settings, low HIV service uptake in a geographically defined area increases the prevalence of high HIV viremia, leading to greater HIV transmission and incident HIV. Methods: A systematic review was conducted to examine the association between population-level measures of HIV viral load and incident HIV infection in generalized and concentrated epidemics. Publications were English, peer-reviewed articles published from January 1, 1995 through February 15, 2019 that explicitly defined HIV viral load and assessed outcomes of HIV recency, incidence, seroconversion, or new diagnosis. Studies sampled general or key populations through population-based surveillance registries, household-based enumeration, cluster sampling, or respondent driven sampling. Descriptive statistics summarized review findings. The Swaziland HIV Incidence Measurement Survey (SHIMS) data were used for the remaining analyses. Using a two-stage cluster-based design, a nationally representative, household-based sample of adults, ages 18-49 years was enrolled from December 2010 to June 2011 in Eswatini. Consenting adults completed an interview and received home-based rapid HIV testing and counseling. All seropositive samples were tested for HIV viral load using the COBAS AmpliPrep/Taqman HIV-1 Test, v 2.0. Adults testing HIV-seronegative were enrolled in a prospective cohort for the direct observation of HIV seroconversion, completing an interview and home-based rapid HIV testing six months later. Multi-level latent class modeling was performed to identify statistically significant combinations of HIV risk factors and to classify the combinations into small area risk profiles. In the cross-sectional sample, linear regression with robust standard errors assessed the correlation between area profiles and places with high levels of uncontrolled HIV infection, or HIV core areas, measured by the area prevalence of detectable virus (≥20 copies/milliliter) among HIV-positive adults and among all adults, regardless of HIV status. In the prospective cohort, generalized linear regression of longitudinal data assessed the association between area profiles and places prone to new HIV infections (i.e., HIV susceptible areas), measured by area-level HIV seroconversions. Results: The systematic review found an evidence base primarily of lower quality studies and inconsistent HIV viral exposure measurement. Overall findings supported a relationship between increasing levels of suppressed HIV in HIV-infected populations and fewer new infections over time. Better quality studies consistently showed higher population viremia (i.e. HIV viral quantity among all persons, regardless of HIV status) associated with HIV incidence in high prevalence populations; population viral load (i.e., HIV viral quantity among only HIV-positive persons) did not show an association with incident HIV in high prevalence, general populations and was inconsistent in key populations. To determine whether area risk profiles can pinpoint HIV core areas, latent class modeling was used to categorize 18,172 adults into one of six HIV risk types. The risk typology, classified through unique combinations of HIV service uptake and sexual risk behaviors, conveyed an adult’s propensity for HIV transmission and/or acquisition risk. The model next identified the area-level composite prevalences of HIV risk types; estimated the three most frequent, unique composite combinations; and categorized them into area risk profiles characterizing HIV risk: low-moderate acquisition risk, moderate acquisition/transmission risk, and high acquisition/transmission risk. The high acquisition/transmission areas comprised the largest proportions of highest risk transmission and acquisition types. The prevalence of detectable viremia progressively increased from low-moderate acquisition, moderate acquisition/transmission, and high acquisition/transmission profiles [17.7%, 25.4%, and 35.1%, respectively]. When compared with low-moderate acquisition areas, the prevalence of detectable viremia was 7.4% [p<.001] higher in moderate acquisition/transmission areas and 17.1% [p<.001] higher in high acquisition/transmission areas. The prevalence of detectable viral load significantly decreased from low-moderate acquisition to moderate acquisition/transmission areas [76.6% versus 68.7%, p<.001], and was significantly higher in high acquisition/transmission areas by 7.3% [p<.001], when compared with low-moderate acquisition areas. To determine whether area risk profiles can predict HIV susceptible areas, a total of 18,172 adults were surveyed of which 4396 [24%] had detectable viremia. 11,880 [96%; n=12,357] HIV-seronegative adults enrolled in the prospective cohort and 11,155 [94%] of them completed an endline visit. Four area profiles were identified, defined by unique patterns in prevalence of HIV viremia and of sexual risk behaviors. The proportion of HIV susceptible areas progressively increased from Profiles A, B, C, and D [14.3%, 21.8%, 24.6%, and 30.8%, respectively]. HIV susceptible areas were more than twice as likely to occur in Profile D than Profile A environments [RR 2.13, 95% confidence interval (CI) (1.13, 4.00); p=0.02]. Profile D areas had prevalences of unknown partner HIV status and detectable viremia at 28% and 24%, respectively. In contrast, Profile A areas had prevalences of only 8% with unknown HIV status and 31% with detectable viremia. Conclusion: This dissertation shows that geographic risk profiles can explain differences in population-level HIV outcomes. Risk factors spatially cluster in predictable, meaningful combinations that can inform an area typology of HIV risk. The co-location of adults predisposed to greater HIV risk may heighten levels of uncontrolled HIV infection, thereby creating potential area sources of ongoing transmission; however, the concurrent levels of other risk factors may have more influence in reducing population-level incidence than previously considered. A composite indicator of contextual HIV risk may reveal places core to HIV transmission and susceptible to HIV acquisition. Such area profiles may help identify the combination of locally specific risk factors that readily promulgate HIV and better inform the design of place-based HIV intervention packages to enhance current strategies towards global HIV control.

Thesis (MSc)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: HIV infection is one of the world’s biggest health problems, with millions of people infected worldwide. HIV infects cells in the immune system, where it primarily targets CD4+ T helper cells and without treatment, the disease leads to the collapse of the host immune system and ultimately death. Mathematical models have been used extensively to study the epidemiology of HIV/AIDS. They have proven to be effective tools in studying the transmission dynamics of HIV. These models provide predictions that can help better our understanding of the epidemiological patterns of HIV, especially the mechanism associated with the spread of the disease. In this thesis we made a functional comparison between existing epidemiological models for HIV, with the focus of the comparison on the force of infection (FOI). The spread of infection is a crucial part of any infectious disease, as the dynamics of the disease depends greatly on the rate of transmission from an infectious individual to a susceptible individual. First, a review was done to see what deterministic epidemiological models exist. We found that many manuscripts do not provide the necessary information to recreate the authors’ results and only a small amount of the models could be simulated. The reason for this is mainly due to a lack of information or due to mistakes in the article. The models were divided into four categories for the analysis. On the basis of the FOI, we distinguished between frequency- or density-dependent transmission, and as a second criterion we distinguished models on the sexual activity of the AIDS group. Subsequently, the models were compared in terms of their FOI, within and between these classes. We showed that for larger populations, frequency-dependent transmission should be used. This is the case for HIV, where the disease is mainly spread through sexual contact. Inclusion of AIDS patients in the group of infectious individuals is important for the accuracy of transmission dynamics. More than half of the studies that were selected in the review assumed that AIDS patients are too sick to engage in risky sexual behaviour. We see that including AIDS patients in the infectious individuals class has a significant effect on the FOI when the value for the probability of transmission for an individual with AIDS is bigger than that of the other classes. The analysis shows that the FOI can vary depending on the parameter values and the assumptions made. Many models compress various parameter values into one, most often the transmission probability. Not showing the parameter values separately makes it difficult to understand how the FOI works, since there are unknown factors that have an influence. Improving the accuracy of the FOI can help us to better understand what factors influence it, and also produce more realistic results. Writing the probability of transmission as a function of the viral load can help to make the FOI more accurate and also help in the understanding of the effects that viral dynamics have on the population transmission dynamics. / AFRIKAANSE OPSOMMING: MIV-infeksie is een van die wêreld se grootste gesondheidsprobleme, met miljoene mense wat wêreldwyd geïnfekteer is. MIV infekteer selle in die immuunstelsel, waar dit hoofsaaklik CD4+ T-helperselle teiken. Sonder behandeling lei die siekte tot die ineenstorting van die gasheer se immuunstelsel en uiteindelik sy dood. Wiskundige modelle word breedvoerig gebruik om die epidemiologie van MIV/vigs te bestudeer. Die modelle is doeltreffende instrumente in die studie van die oordrag-dinamika van MIV. Hulle lewer voorspellings wat kan help om ons begrip van epidemiologiese patrone van MIV, veral die meganisme wat verband hou met die verspreiding van die siekte, te verbeter. In hierdie tesis het ons ‘n funksionele vergelyking tussen bestaande epidemiologiese modelle vir MIV gedoen, met die fokus van die vergelyking op die tempo van infeksie (TVI). Die verspreiding van infeksie is ‘n belangrike deel van enige aansteeklike siekte, aangesien die dinamika van die siekte grootliks afhang van die tempo van oordrag van ‘n aansteeklike persoon na ‘n vatbare persoon. ‘n Oorsig is gedoen om te sien watter kompartementele epidemiologiese modelle alreeds bestaan. Ons het gevind dat baie van die manuskripte nie die nodige inligting voorsien wat nodig is om die resultate van die skrywers te repliseer nie, en slegs ‘n klein hoeveelheid van die modelle kon gesimuleer word. Die rede hiervoor is hoofsaaklik as gevolg van ‘n gebrek aan inligting of van foute in die artikel. Die modelle is in vier kategorieë vir die analise verdeel. Op grond van die TVI het ons tussen frekwensie- of digtheidsafhanklike oordrag onderskei, en as ‘n tweede kriterium het ons die modelle op die seksuele aktiwiteit van die vigs-groep onderskei. Daarna is die modelle binne en tussen die klasse vergelyk in terme van hul TVIs. Daar is gewys dat frekwensie-afhanklike oordrag gebruik moet word vir groter bevolkings. Dit is die geval van MIV, waar die siekte hoofsaaklik versprei word deur seksuele kontak. Die insluiting van die vigs-pasiënte in die groep van aansteeklike individue is belangrik vir die akkuraatheid van die oordrag-dinamika van MIV. Meer as helfte van die uitgesoekte studies aanvaar dat vigs-pasiënte te siek is om betrokke te raak by riskante seksuele gedrag. Ons sien dat die insluiting van vigs-pasiënte in die groep van aansteeklike individue ‘n beduidende uitwerking op die TVI het wanneer die waarde van die waarskynlikheid van oordrag van ‘n individu met vigs groter is as dié van die ander klasse. Die analise toon dat die TVI kan wissel afhangende van die parameter waardes en die aannames wat gemaak is. Baie modelle voeg verskeie parameter waardes bymekaar vir die waarskynlikheid van oordrag. Wanneer die parameter waardes nie apart gewys word nie, is dit moeilik om die werking van die TVI te verstaan, want daar is onbekende faktore wat ‘n invloed op die TVI het. Die verbetering van die akkuraatheid van die TVI kan ons help om die faktore wat dit beïnvloed beter te verstaan, en dit kan ook help om meer realistiese resultate te produseer. Om die waarskynlikheid van oordrag as ‘n funksie van die viruslading te skryf kan help om die TVI meer akkuraat te maak en dit kan ook help om die effek wat virale dinamika op die bevolkingsoordrag-dinamika het, beter te verstaan.