Toxoplasma gondii is a single-celled parasite that has a wide range of hosts including humans. A cross-sectional survey was conducted to investigate T. gondii seroprevalence and associated risk factors in small ruminants, pigs, poultry and cats in the Oliver Reginald Tambo District in the Eastern Cape in South Africa between June 2016 and October 2016. Household-level and animal-level data were collected using a close-ended questionnaire. One sample of each present species was collected in each household. The Toxoreagent ®, Mast Group, United Kingdom, latex agglutination test, was used for T. gondii antibody detection. Positive samples had agglutination patterns at dilutions of 1:64 or greater, except for chickens, whose cut off titre was 1:32. A household was classified as T. gondii seropositive if at least one species tested positive. The study revealed that 78 out of 121 sheep (64.46%), 69 out of 128 goats (53.91%), 36 out of 106 pigs (33.96%), 35 out of 109 cats (32.11%) and 46 out of 137 chickens (33.58%) were seropositive for the parasite. Seropositivity was assessed for association with potential risk factors. Age, location, climate, animal production system, rodent control, cat-feed access and cat faecal disposal were found to be significantly associated with seropositivity using the Chi-Squared test or odds ratio confirmed by the Fisher's exact test. The relatively high seroprevalence of T. gondii detected in this study suggests that the infection T. gondii poses a substantial public health risk through the consumption of infected raw or undercooked meat infected with T.gondii cysts as well as contact with cat faeces infected with T. gondii oocysts. / Dissertation (MSc)--University of Pretoria, 2016. / Veterinary Tropical Diseases / MSc / Unrestricted

HIV and AIDS pandemic have been declining in South Africa. HIV and AIDS affect individuals, families, organizations and the communities at large. While the roll out of the antiretroviral treatment (ART) has brought much excitement and hope to both patients and the health practitioners, it has also brought challenges (Maskew, Macphail, Menez & Rubel, 2007:853). In order for ART to be effective patients need to adhere to antiretroviral treatment, thus adherence is a critical component of ART. Patients who discontinue treatment are at high risk of illness and death because of AIDS related diseases or developing drug resistant virus. With a better understanding of the reasons for defaulting antiretroviral treatment interventions can be designed to improve adherence to antiretroviral treatment. Thus the purpose of this study was to explore the reasons why HIV and AIDS infected patients default antiretroviral treatment because adherence to ART is of utmost important. Within the context of qualitative and applied research the researcher utilized the collective case study design. Semi structured interviewing was used as data collection method to elicit qualitative information on the reasons why patients default ART. The main research question that was put forward to all participants was: What are your reasons for defaulting ART? The participants in this study were patients who have default their ART during 2012. By using systematic sampling fourteen participants from Thekganang ARV Clinic in Seshego District Hospital, Limpopo province, were selected to form a sample for this study. Some conclusions based on the findings were that: The participants were knowledgeable about the basic facts of HIV and AIDS and they had a good understanding about the importance of adherence even though they defaulted their antiretroviral treatment. The use of ART may also be challenging to individuals. The findings of this study were that not all participants in the study experienced challenges with taking ART. Those who experienced challenges included fear of disclosing HIV status, fear of stigmatization and physical challenges due to ill health. Regarding the reasons for defaulting ART, participants’ reasons for defaulting antiretroviral treatment were similar although some of the reasons applied to only one participant. Participants’ reasons for treatment default were classified into socio-economic factors, patient related, psychological related and medication related factors. Socio- economic factors included shortage of food in the household and lack of money for transport to attend clinic appointments. Patient related factors included substance abuse, lost appointment cards, participants were too busy with personal issues and relocation to another area of residence. Psychological factors that contributed to non-adherence to treatment were depression and denial. Medical related factor voiced was that participant was too confused about the drug regimen. Most participants were satisfied with the services in Thekganang ARV clinic although some participants raised concerns about staff attitudes and long queue. The findings will assist the hospital management and the clinic staff to make informed decisions about the management of defaulters in the clinic. The study was concluded with the relevant recommendations to the ART facilities. The recommendations included implementation of the multi-disciplinary centred approach, establishing patient education programmes and on-going support services to patients who fail to adhere to treatment. Future research studies should determine the prevalence of drug resistant HIV patients in the ART facilities and the development of a systematic method of capturing ‘‘lost to follow up’’ patients who pass away within hospitals. / Dissertation (MA)--University of Pretoria, 2014. / lk2014 / Social Work and Criminology / MA / Unrestricted

>Magister Scientiae - MSc / Background and Aims Human Immunodeficiency Virus (HIV) type 1 group M subtype C (HIV-1C) accounts for nearly half of global HIV-1 infections, with South Africa (SA) being one of the countries with the highest infection burden. In recent years, SA has made great strides in tackling its HIV epidemic, resulting in the country being recognized globally as the one sub-Saharan country with the largest combination antiretroviral therapy (cART) programme. Regardless of the potency of cART, the efficacy of the treatment is limited and hampered by the emergence of drug resistance. The majority of research on HIV-1 infections, effect of antiretroviral (ARV) drugs and understanding resistance to ARV drugs has been extensively conducted, but mainly on HIV-1 subtype B (HIV-1B), with less information known about HIV-1C. HIV-1’s viral Integrase (IN) enzyme has become a viable target for highly specific cART, due to its importance in the infection and replication cycle of the virus. The lack of a complete HIV-1C IN protein structure has negatively impacted the progress on structural studies of nucleoprotein reaction intermediates. The mechanism of HIV-1 viral DNA’s integration has been studied extensively at biochemical and cellular levels, but not at a molecular level. This study aims to use in silico methods that involve molecular modeling and molecular dynamic (MD) simulations to prioritize mutations that could affect HIV-1C IN binding to DNA and the IN strand-transfer inhibitor (INSTI) dolutegravir (DTG). The purpose is to help tailor more effective personalized treatment options for patients living with HIV in SA. This study will in part use patient derived sequence data to identify mutations and model them into the protein structure to understand their impact on the HIV-1C IN protein structure folding and dynamics. Methods Our sample cohort consisted of 11 sample sequences derived from SA HIV-1 treatmentexperienced patients who were being treated with the INSTI raltegravir (RAL). The sequences were submitted to the Stanford HIV resistance database (HIVdb) to screen for any new/novel variants resulting from possible RAL failure. Some of these new variants were analyzed to analyse their effect, if any, on the binding of DTG to the HIV-1C IN protein. Additionally, an HIV-1C IN consensus sequence constructed from SA’s HIV-1 infected population was used to model a complete three-dimensional wild type (WT) HIV-1C IN homology model. All samples were sequenced by our collaborators at the Division of Medical Virology, Stellenbosch University together with the National Health Laboratory Services (NHLS), SA. The HIV-1CZA WT-IN protein enzyme was predicted using SWISS-MODEL, and the quality of the resulting model validated. Various analyses were conducted in order to study and assess the effect of the selected new variants on the protein structure and binding of DTG to the IN protein. The mutation Cutoff Scanning Matrix (mCSM) program was used to predict protein stability after mutation, while PyMol helped to study any changes in polar contact activity before and after mutation. PyMol was also used to generate four mutant HIV-1C IN complex structures and these structures together with the WT IN were subjected to production MD simulations for 150 nanoseconds (ns). Trajectory analyses of the MD simulations were also conducted and reported. Results A total of 21 new variants were detected in our sample cohort, from which only six were chosen for further analyses within the study. A homology model of HIV-1C IN was successfully constructed and validated. The structural quality assessment indicated high reliability of the HIV-1C IN tetrameric structure, with more than 90.0% confidence in modelled regions. Of the six selected variants, only one (S119P) was calculated to be slightly stabilizing to the protein structure, with the other five found to be destabilizing to the IN protein structure. Variant S119P showed a loss in polar contacts that could destabilize the protein structure, while variant Y143R, resulted in the gain of polar contacts which could reduce flexibility of the 140’s region affecting drug binding. Similarly, mutant systems P3 (S119P, Y143R) and P4 (V150A, M154I) showed reduced hydrogen bond formation and the weakest non-bonded pairwise interaction energy. These two systems, P3 and P4, also showed significantly reduced to none polar contacts between DTG, magnesium (MG) ions and the IN protein, compared to the WT IN and P2 mutant IN systems. Interestingly, the WT structure and systems P1 (I113V) and P2 (L63I, V75M, Y143R) showed the highest non-bonded interaction energy, compared to systems P3 and P4. This was further supported by the polar interaction analyses of simulation clusters from the WT IN and mutant IN system P2 (L63I, V75M, Y143R), which were the only protein structures that formed polar contacts with DTG, MG ions and DDE motif residues, while P1 only made contacts with DNA and IN residues. Conclusion Findings from this study leads to a conclusion that double mutants (S119P, Y143R) and (V150A, M154I) may result in a reduction in the efficacy of DTG, especially when in combination. Furthermore, variants identified in systems P1 and P2 may still allow for effective DTG binding to IN and outcompete viral DNA for host DNA to prevent strand transfer. To the best of our knowledge, this is the first study that uses the consensus WT HIV1C IN sequence to build an accurate 3D homology model to understand the effect of less frequently detected/reported variants on DTG binding in a South African context. https://etd.

The human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) that subsequently develops remain major health concerns even after three decades since the first cases were reported. Successful therapeutic measures to address HIV/AIDS consist mostly of combinations of drugs targeting viral enzymes including reverse transcriptase (RT), protease (PR) and integrase (IN) as well as entry steps of the viral life cycle. The remarkable benefits (e.g. improved quality of life) derived from the use of these agents are unfortunately limited by toxicity to the host and the development of drug resistant viral strains. Drug resistance limits the repertoire of drug combinations available. Unfortunately, because latent forms of the virus exists, therapy has to be life-long and with new infections occurring every day, resistant strains tend to spread. To circumvent these problems, new drugs that inhibit resistant strains or work against new viral targets have to be developed. The history of gold compounds as potential inhibitors of HIV prompted this study in which twenty seven compounds consisting of gold(I), gold(III) and precursors from five classes were tested for drug-likeness, anti-HIV and immunomodulatory effects using wet lab and in silico methodologies. Cytotoxicity determination was done using viability dyes and flow cytometry. Cell proliferation profiles were monitored using the carboxyflourescein succinimidyl ester dye dilution technology and a real time cell analyser for confirming viability dye findings. The compounds’ effects on viral enzymes was determined using direct enzyme assays and in silico molecular modelling techniques. H and P nuclear magnetic resonance spectroscopy studies for determining stability revealed that the backbone chemical shifts of the compounds were relatively unchanged after one week (-20 and 37 ºC) when dissolved in dimethylsulfoxide. Eight of the gold compounds had drug-like properties comparable to clinically available drugs when in silico predictions were performed. The 50% cytotoxic dose of the compounds in human cells was between 1 and 20 μM (clinically relevant concentrations for gold compounds). Three gold(I) compounds inhibited viral infectivity at non-toxic concentrations and two gold(III) compounds did so at cytostatic (anti-proliferative mechanism that is also antiviral) concentrations. In the immunomodulatory assay, cytokine levels were altered by five compounds with one gold(I) and a gold(III) compound significantly reducing the frequency of CD4+ cells (an anti-viral function) from HIV+ donors (p= 0.005 and 0.027 respectively) when multi-parametric flow cytometry was performed. Inhibition of RT activity was predicted in in silico studies to be through interactions with the ribonuclease (RNase) H site although with poor stereochemical orientation while favourable binding predictions with the IN cofactor binding site were observed for some gold(III) complexes. Compounds predicted to interact with the RNase H site of RT and the IN cofactor site require structural modification to improve drug-likeness and binding affinity. The drug-like compound(s) which inhibited viral infectivity and lowered CD4+ cell frequency have potential for incorporation into virostatic cocktails (combination of cytostatic and directly anti-viral agent). Cytostatic agents are known to be less prone to drug resistance and because they lower CD4+ cell frequency, such compounds can potentially limit HIV immune activation. / Thesis (PhD)--University of Pretoria, 2011. / Biochemistry / unrestricted

Magister Public Health - MPH / South Africa’s Infant and Young Child Feeding (IYCF) policy guidelines of 2013 and its 2017 amendments recommend that mothers, including those living with HIV, exclusively breastfeed their infants until 24 months of age, followed by their gradual weaning. The 2013 changed policy guidelines occurred to align with global WHO recommendations of six-month exclusive breastfeeding for all HIV positive mothers, and consequently no longer recommended free formula feed as an option for HIV-positive mothers attending public sector services, except in limited circumstances. Despite these policy guidelines, less than a third of South African mothers exclusively breastfeed their infants. The other two thirds of mothers either formula feed or mixed feed their infants. Mixed feeding or exclusive breastfeeding by HIV positive mothers who have either not been on antiretroviral therapy (ART) long enough or are insufficiently adherent to ART to suppress their viral loads, can potentially lead to increased risk of Mother to Child Transmission (MTCT) of the Human Immunodeficiency Virus (HIV). Since healthcare workers (HCWs) play a key role in promoting the IYCF policy guidelines and encouraging its practice among HIV-positive mothers, it is crucial to determine the extent to which HCWs understand and subscribe to this important policy. Using purposeful sampling and in-depth qualitative interview techniques, this qualitative study explored the attitudes of HCWs towards different infant feeding options, especially for HIV positive mothers, against the background of their understanding of the changes in IYCF policy guidelines between 2013 and 2017. The participants in this study included ten HCWs selected from three primary health care facilities in Khayelitsha (Western Cape, South Africa), and two programme coordinators based at the Western Cape’s Department of Health Khayelitsha substructure office. By interviewing this diverse sample of HCW cadre, the study aimed to explore their perceptions related to the factors which facilitate IYCF policy implementation versus those that hinder the implementation of this policy. The findings revealed that HCWs interviewed had good overall familiarity with the IYCF policy guidelines. However, their depth of understanding and acceptability of the policy varied, especially in the context of high HIV MTCT risk. Suboptimal implementation of the policy occurred due to inadequate policy dissemination, diverse views on the limitations of the policy, such as the promotion of only exclusive breastfeeding as an option and an unclear rationale for recent policy changes. Additionally, HCWs high workload and insufficient training on the changed 2017 guidelines were identified as barriers to effectively implementing the new infant feeding policy guidelines. HCW further perceived that personal, socio-cultural and health system factors influenced new mothers’ decisions and/or ability to breastfeed. These findings highlight that improved policy dissemination strategies and training should be used to increase HCWs knowledge regarding infant feeding counselling content, including HIV MTCT risk. Western Cape Department of Health alignment and implementation of relevant National Department of Health HIV policies should occur to decrease MTCT risk while breastfeeding. Peer support groups could provide maternal support for continued postnatal ART adherence and for sustained safer feeding practices. Finally, while exclusive breastfeeding is the optimal feeding choice generally for mothers, future revision of the 2017 IYCF policy should consider allowing HCW to act more flexibly in the maternal guidance they provide on infant feeding options. This could allow greater discretion for HCW in infant feeding counselling of mothers, particularly for those women who are HIV positive. This would promote improved patient-centred counselling that takes into account both maternal socio-cultural context and the right to make individualised decisions regarding infant feeding.

Master of Public Health - MPH / South Africa’s Infant and Young Child Feeding (IYCF) policy guidelines of 2013 and its 2017 amendments recommend that mothers, including those living with HIV, exclusively breastfeed their infants until 24 months of age, followed by their gradual weaning. The 2013 changed policy guidelines occurred to align with global WHO recommendations of six-month exclusive breastfeeding for all HIV positive mothers, and consequently no longer recommended free formula feed as an option for HIV-positive mothers attending public sector services, except in limited circumstances. Despite these policy guidelines, less than a third of South African mothers exclusively breastfeed their infants. The other two thirds of mothers either formula feed or mixed feed their infants. Mixed feeding or exclusive breastfeeding by HIV positive mothers who have either not been on antiretroviral therapy (ART) long enough or are insufficiently adherent to ART to suppress their viral loads, can potentially lead to increased risk of Mother to Child Transmission (MTCT) of the Human Immunodeficiency Virus (HIV). Since healthcare workers (HCWs) play a key role in promoting the IYCF policy guidelines and encouraging its practice among HIV-positive mothers, it is crucial to determine the extent to which HCWs understand and subscribe to this important policy. Using purposeful sampling and in-depth qualitative interview techniques, this qualitative study explored the attitudes of HCWs towards different infant feeding options, especially for HIV positive mothers, against the background of their understanding of the changes in IYCF policy guidelines between 2013 and 2017. The participants in this study included ten HCWs selected from three primary health care facilities in Khayelitsha (Western Cape, South Africa), and two programme coordinators based at the Western Cape’s Department of Health Khayelitsha substructure office. By interviewing this diverse sample of HCW cadre, the study aimed to explore their perceptions related to the factors which facilitate IYCF policy implementation versus those that hinder the implementation of this policy. The findings revealed that HCWs interviewed had good overall familiarity with the IYCF policy guidelines. However, their depth of understanding and acceptability of the policy varied, especially in the context of high HIV MTCT risk. Suboptimal implementation of the policy occurred due to inadequate policy dissemination, diverse views on the limitations of the policy, such as the promotion of only exclusive breastfeeding as an option and an unclear rationale for recent policy changes. Additionally, HCWs high workload and insufficient training on the changed 2017 guidelines were identified as barriers to effectively implementing the new infant feeding policy guidelines. HCW further perceived that personal, socio-cultural and health system factors influenced new mothers’ decisions and/or ability to breastfeed. These findings highlight that improved policy dissemination strategies and training should be used to increase HCWs knowledge regarding infant feeding counselling content, including HIV MTCT risk. Western Cape Department of Health alignment and implementation of relevant National Department of Health HIV policies should occur to decrease MTCT risk while breastfeeding. Peer support groups could provide maternal support for continued postnatal ART adherence and for sustained safer feeding practices. Finally, while exclusive breastfeeding is the optimal feeding choice generally for mothers, future revision of the 2017 IYCF policy should consider allowing HCW to act more flexibly in the maternal guidance they provide on infant feeding options. This could allow greater discretion for HCW in infant feeding counselling of mothers, particularly for those women who are HIV positive. This would promote improved patient-centred counselling that takes into account both maternal socio-cultural context and the right to make individualised decisions regarding infant feeding.

Sammanfattning Bakgrund: Hiv är ett globalt problem som sedan tidigt 1980-tal spridit sig världen över. Infektionssjukdomen kan inte botas, men med en välinställd läkemedelsbehandling kan människor leva ett fullgott liv utan att smitta. Sjukdomen var tidigare oerhört dödlig och smittsam, vilket skapade ett stort stigma hos allmänheten. Personer med Hiv har blivit utsatta för diskriminering där sjuksköterskor och allmänheten inte velat ha någon fysisk kontakt med dem. Det fanns en ovilja hos sjuksköterskor att vårda patienter med Hiv. Det är betydande att sjuksköterskan har ett holistiskt synsätt och bedriver en personcentrerad vård för ett gott omvårdnadsmöte. Syfte: Syftet med studien var att beskriva hur patienter med Hiv upplevde omvårdnadspersonalens bemötande inom hälso-och sjukvård. Metod: En allmän litteraturstudie baserad på tio vetenskapliga artiklar med kvalitativ ansats. Databaser som användes vid artikelsökningen var Cinahl, PubMed och PsycINFO. Resultat: Resultatet bestod av fem huvudkategorier; Upplevelsen av acceptans och stöd, Upplevelsen av att inte vara prioriterad, Upplevelsen av att vara dömd, Upplevelsen av att bli exponerad och Upplevelsen av att inte bli bekräftad. Resultatet visade att stigmatisering var vanligt förekommande inom hälso- och sjukvården och att patienterna kunde känna sig exponerade vid sekretessbrott. Diskussion: Metoddiskussionen utgick från kvalitetsbegreppen Tillförlitlighet, Verifierbarhet, Pålitlighet och Överförbarhet. Resultatdiskussionen bestod av tre centrala fynd från resultatet, vilka var Upplevelsen av acceptans och stöd, Upplevelsen av att vara dömd och Upplevelsen av att bli exponerad. Upplevelsen av att vara dömd och upplevelsen av att vara exponerad diskuteras utifrån McCormack & McCance teori om personcentrerad vård och upplevelsen av acceptans och stöd diskuteras utifrån Halldórsdottirs teori Caring and Uncaring. Båda teorierna diskuteras utifrån hur de kan ligga till grund för ett gott bemötande. Etiska aspekter och samhällsperspektiv diskuteras också

Untreated human immunodeficiency virus (HIV) can be complicated by opportunistic infections, including disseminated histoplasmosis (DH). Although endemic to portions of the United States and usually benign, DH can rarely act as an opportunistic infection in immunocompromised patients presenting with uncommon complications such as acute kidney injury and idiopathic thrombocytopenic purpura. We report a rare presentation of DH presenting with acute kidney injury and immune thrombocytopenic purpura in an immunocompromised patient with HIV.

Purpose of Review: Recent technological developments have vastly improved our ability to study the host microbiome and its role in many disease states. Numerous other reviews have contributed to our understanding of single viruses and gut microbiota or immunological outcomes. Here, we report, in aggregate, the newest data on genital microbiota interactions with the three most common viral STIs. Recent Findings: Four themes emerge: (1) the repeatability of specific community state types corresponding with infection risk, (2) a role for the microbiota as both therapeutic target and major player in treatment efficacy, (3) a need for models in which to study the mechanisms at play in microbiota/virus interactions, and (4) the impact of microbiota populating external genitalia on viral transmission. Summary: The studies reviewed herein suggest a convoluted interplay between host microbiota and viral STIs. More mechanistic studies are needed in order to leverage these interactions to improve prevention and treatment strategies.

Thesis (MPH.) -- University of Limpopo, 2020 / Background: In South Africa, the Choice on Termination of Pregnancy Act (CTOP) (No. 92 of 1996) promotes a woman's reproductive right and choice to have an early, safe and legal abortion. Pregnancy termination among young women constitutes a public health problem particularly in South Africa where high prevalence of abortion has been recently recorded. HIV acquisition is increased two to four-fold during pregnancy, due to biological and behavioural factors including immunological changes, hormonal changes affecting the genital tract mucosa, higher frequency of unprotected sex and incident sexually transmitted infections (STIs) during pregnancy. There is a growing interest in exploring maternal mental health effects of unintended pregnancies. However, the evidence base from a small number of available studies is characterized by considerable variability, inconsistency and inconclusive findings. Therefore, the primary objective of this study was to investigate the prevalence of HIV and its association with termination of pregnancy at Seshego Zone 4 clinic in Limpopo Province. Methodology: A cross-section descriptive retrospective review study in which convenience sampling of the records of women who terminated pregnancies was used in this study. The key variable of interest in this study was HIV results and all patients records without evidence of HIV testing, and the associated results were excluded. A self-designed data extraction tool was used to extract the data from patients records and tool covered variables such as the age of the women, educational status, marital status, occupational status, year and month of termination of pregnancy, gestational age, parity, and gravidity, method of contraceptive used, HIV status, ARV and ARV regimens. Data analysis was done using the STATA statistical software version 12 for Windows (STATA Corporation, College Station, Texas). vi Results: The mean age was 24.98 years SD±14.4 and majority of women who terminated pregnancies were in the age group 20 – 24 years at 35.7% and the least number of women who terminated pregnancies were in the age groups ≥ 40 years and ≤ 14 years at 2.3% and 0.3% respectively. Majority of the women who terminated pregnancies had parity of 1 – 2 at 47.4% followed by parity of zero at 42.3% and 3 – 4 at 9.9%. Majority of the women who terminated pregnancies were in gravida 1 at 42.8% followed by those with gravida 2 at 27.1% and those who were pregnant between the 3rd and 4th time were 26.9%. There was a statistical significance difference (p<0.001) of the use of contraceptives by age groups and also in relation to parity and similarly to gravidity. The prevalence of HIV amongst women who terminated pregnancies in the current study was found to be 11.6% and this was high in 2018 at 10.5% followed by 2019, 2015 and 2016 at 10.3%, 9.2% and 9.1% respectively. The prevalence of HIV amongst women who terminated pregnancies increased with increasing level of education from 4.1% amongst women who had primary or no educational level the followed by 9,0% and 13.6% in women who had secondary and tertiary educational level respectively. The risk of women who terminate pregnancies being HIV positive in the current study increased significantly with increasing age as older women were 1.9 times more likely to be HIV positive as compared to younger ones (p=0.004) Conclusion: The findings of this study highlight the need to address the structural socio-economic drivers of the HIV epidemic among women of child-bearing age. Women of child-bearing age in this setting have large unmet reproductive health needs. Structural interventions, such as increasing contraceptive use which may be useful for reducing the burden of unplanned pregnancies. Key concepts Human immunodeficiency virus, Acquired immunodeficiency syndrome, Termination of pregnancy, Parity and Gravidity.