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Since the first detected cases of Middle East Respiratory Syndrome Coronavirus (MERS-CoV), a respiratory virus capable of causing severe human illness, surveillance and research have focused on identification of the source of primary human MERS-CoV infections. Within the One Health framework which recognizes the interconnectedness of human, animal, and environmental health, various animal hosts were investigated as sources of human infection because most emerging infectious diseases are zoonoses – pathogens spilling over from an animal host to a human. A systematic literature review was conducted to synthesize knowledge about MERS-CoV infections in livestock animals and zoonotic transmission of MERS-CoV to humans. Dromedary camels are the presumptive source of primary human MERS-CoV infections, but the importance, frequency, and specific mechanisms of camel-to-human MERS-CoV transmission have not been well characterized. Further, it is unknown what potential barriers will be faced when implementing basic biosecurity interventions to prevent zoonotic transmission at occupational sites where individuals regularly work or interact with dromedary camels. This dissertation addressed these knowledge gaps through a study of MERS-CoV serology and knowledge, attitudes, and beliefs about camel-to-human disease risks and basic biosecurity interventions in Jordan. This study detected individuals with low MERS-CoV neutralizing antibody titers in Jordan and found an association between regular work or interaction with dromedary camels or their living environments and evidence of MERS-CoV infection. Specific behavioral practices were not associated with evidence of MERS-CoV infection among those who regularly work or interact with dromedary camels or their living environments in Jordan. The study also identified multiple important barriers that may be faced when implementing basic biosecurity interventions in this population, including personal protective equipment (PPE) use and frequent handwashing. There were widespread ingrained beliefs that dromedary camels cannot transmit disease to humans and that camel milk and camel urine are beneficial to human health. Among camel workers, reported PPE use was low and frequent handwashing was uncommon. Only a few camel workers felt they would use PPE even if made freely available at their place of work. In conclusion, this dissertation provides further evidence that dromedary camel exposure is an important pathway in the epidemiology of primary human MERS-CoV infections in Jordan. The findings also support the notion that an intervention that simply provides basic biosecurity materials such as PPE and handwashing stations is likely to be ineffective in this population, and that identified barriers should be addressed to motivate behavioral change. Future studies are proposed including a longitudinal cohort study of individuals at risk for MERS-CoV that can detect individual seroconversion over time, track antibody responses among those who seroconvert, and evaluate key sub-exposures among those who are occupationally exposed to dromedary camels; as well as a pilot study to evaluate the feasibility, acceptability, and sustainability of a multifaceted biosecurity intervention that provides materials as well as training and education targeting the knowledge, attitude, and belief barriers identified.

Thesis (MPH.) -- University of Limpopo, 2021 / Introduction: HIV/AIDS remains a disease of public health importance and mother-to-child transmission (MTCT) is one of the major problems. Sub-Saharan Africa is the most severely affected region, accounting for more than 90 percent of paediatric HIV infections. Most of these infections occurred during pregnancy, delivery or breastfeeding making the prevention of mother-to-child transmission (PMTCT) a public health priority. Over the last few years, efforts have been made in Sub-Saharan countries to improve PMTCT and the success of prevention of mother‐to‐child transmission of HIV (PMTCT) is dependent upon high retention of mother‐infant pairs within the PMTCT cascade. Assessing the risk factors for MTCT will help to decrease child morbidity and mortality and strengthen PMTCT programs as there is dearth of evidence regarding factors determining MTCT HIV infection to infants born to HIV positive mothers. The purpose of this study was to investigate the determinants for the human Immunodeficiency Virus positivity rates in the Greater Letaba Municipality. The study objectives were to describe the demographic characteristics of mothers and babies who tested polymerase chain reaction test (PCR)-positive in the Greater Letaba Municipality during the two-year period from 2015 to 2016, in order to determine maternal and neonatal factors associated with high positive PCR; and to determine health system-related factors associated with a high positive PCR result. Methodology The current study followed a quantitative approach in which convenient and purposive sampling was used, focusing on records of infants born from HIV-positive women in all clinics at Greater Letaba Municipality were reviewed. All records of infants who were tested for HIV and the PCR results were positive from birth up to 12 months of age were retrospectively reviewed and for the health care workers, all nurses working as managers of a clinic were interviewed. The Statistical Package for the Social Sciences (SPSS) version 23 computer software and Stata 15 was used. for comparison of categorical variables was done using a Chi-Squared test, whereas continuous variables were compared using a t-test and P-value of <0.05 was considered significant. To determine maternal and neonatal factors associated with high positive PCR, Factor analysis was used with rotated factor loadings done using the Varimax method. Results: A total of 107 records were retrieved and audited. Fisher’s exact test was used to determine the relationship between selected variables, where p<0.05 was set as level of significance. The findings reveal that the number of infants exposed to HIV during pregnancy has steadily increased. The current study further indicates that health system factors such as unskilled or untrained NIM-ART nurses in the facilities is a contributory factor to infant’s positivity rate in Greater Letaba hospital. Equal proportions of both male and female babies were found to be PCR positive at 6 weeks. The study further revealed that the highest proportion of the mothers who gave birth to PCR positive babies for the reporting period were married mothers, in the age group 25-29 years (46.1%). The second largest proportion of mothers who gave birth to PCR positive babies were single mothers in the age group 25-29 years (38.4%). The results show that high PCR positivity can be attributed to about 5 main Factors namely: maternal antenatal history (22% contribution to total variance), maternal HIV care history (18% contribution to total variance), measures of adherence to treatment (17% contribution to total variance), maternal exposure to HIV (14% contribution to total variance) and lastly the ART regimen (12% contribution to total variance). Conclusion: The study findings revealed that there is still vertical transmission of HIV to infants and the prevalence of HIV among infants born from seropositive mothers despite the availability of the latest Prevention of Mother to Child Transmission (PMTCT) Guidelines in all health care facilities. Even though transmission is reduced to the meaningful number (< 5%), there are still appropriate measures that should be taken to reduce the transmission of HIV from mothers to infants. The delayed diagnosis, adherence to ART by mothers, infant ARV prophylaxis at birth and feeding practices contributed the vertical transmission of HIV to infants. Strengthening of the PMTCT of HIV programme, increasing antenatal HIV screening and linking it to care and treatment of HIV positive mothers to obtain zero infant HIV prevalence in the region. Infant prophylaxis and maternal PMTCT interventions should be provided to all exposed infants and mothers based on the guidelines by the health institutions. Nurse-initiated management of antiretroviral treatment (NIM-ART) training of professional nurses is being offered by the Department of Health in South Africa, but it does not yield positive results as far as the PMTCT is concerned. This may be due to shortage of staff, especially trained professional nurses (PN), as well as the workload. Key concepts: Infant and Human immune deficiency virus

Indiana University-Purdue University Indianapolis (IUPUI) / With effective antiretroviral therapy (ART), cardiovascular diseases (CVD), are emerging as a major cause of morbidity and death in the aging population with HIV infection. Although this increase in CVD could be partially explained by the toxic effects of combined anti-retroviral therapy (ART), more recently, HIV infection has emerged as an independent risk factor for CVD. However, it is unclear how HIV can contribute to CVD in patients on ART, when viral titers are low or non-detectable. Here, we provide several lines of evidence that HIV-Nef, produced in infected cells even when virus production is halted by ART, can lead to endothelial activation and dysfunction, and thus may be involved in CVD. We demonstrate that HIV-infected T cell-induced endothelial cell activation requires direct contact as well as functional HIV-Nef. Nef protein from either HIV-infected or Nef-transfected T cells rapidly transfers to endothelial cells while inducing nanotube-like conduits connecting T cells to endothelial cells. This transfer or transfection of endothelial cells results in endothelial apoptosis, ROS generation and release of monocyte attractant protein-1 (MCP-1). A Nef SH3 binding site mutant abolishes Nef-induced apoptosis and ROS formation and reduces MCP-1 production in endothelial cells, suggesting that the Nef SH3 binding site is critical for Nef effects on endothelial cells. Nef induces apoptosis of endothelial cells through both NADPH oxidase- and ROS-dependent mechanisms, while Nef-induced MCP-1 production is NF-kB dependent. Importantly, Nef can be found in CD4 positive and bystander circulating blood cells in patients receiving virally suppressive ART, and in the endothelium of chimeric SIV-infected macaques. Together, these data indicate that Nef could exert pro-atherogenic effects on the endothelium even when HIV infection is controlled and that inhibition of Nef-associated pathways may be promising new therapeutic targets for reducing the risk for cardiovascular disease in the HIV-infected population.