In the rural areas of Kwa Zulu Natal small scale farming is the main agricultural activity, which is often carried out in addition to other employment taken on in another location by at least one member of the household. Although Veterinary services (VS) was aware of several diseases occurring in this area and has implemented a dipping strategy for tick borne diseases as well as a regional annual vaccination campaign for Rabies, Anthrax and Black quarter, uncertainty remained about the relative importance of other diseases such as brucellosis, leptospirosis and enzootic bovine leucosis. Further it was of interest to investigate the serological resistance of cattle against the tick borne diseases babesiosis and anaplasmosis. In addition to this veterinary services wanted to increase their understanding of the perceptions and practices of local cattle owners that were relevant for the context of disease control. A serological survey of cattle was carried out between March 2001 and December 2003 to determine the prevalence of the above-mentioned diseases. The survey was designed as a two-stage survey, considering the diptank as the primary sampling unit. The conduction of the questionnaire survey was based on a convenience sample and took place during the dipping procedure. The apparent prevalence at district level was adjusted for clustering, and diagnostic test sensitivity and specificity and displayed in maps. The mean true prevalence of brucellosis varied from zero to 15.8 percent in the north eastern region with the large majority of the districts being disease free. Enzootic Bovine Leukosis (EBL) was widely present in the province at generally low prevalences, except in the central region where the highest prevalence at district level was recorded to be 70 percent. Leptospirosis also occurred frequently with the highest prevalence noted being 62 percent at district level. The southern regions showed a higher leptospirosis prevalence than other areas of the province, while in some of the northern and western districts a lower prevalence is noted. The encountered servovars were pomona, which occurred most frequently, tarrasovi, bratislava, hardjo, canicola and icterohaemorrhagica. While Babesia bovis and anaplasmosis occurred at a high prevalence throughout the province, B. bigemina was found to be much less established and is absent from many of the northern districts. Most prevalences calculated at district level do show large confidence intervals due to uncertainty that arose from the sampling frame and should be interpreted with care. / Dissertation (MSc (Production Animal Studies))--University of Pretoria, 2007. / Production Animal Studies / MSc / unrestricted

Staying current on literature related to antimicrobial stewardship can be challenging given the ever-increasing number of published articles. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship–related peer-reviewed literature that detailed an actionable intervention for 2019. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the actionable intervention used by antimicrobial stewardship programs to provide key stewardship literature for teaching and training and to identify potential intervention opportunities within one’s institution.

With an increasing number of antimicrobial stewardship-related articles published each year, attempting to stay current is challenging. The Southeastern Research Group Endeavor (SERGE-45) identified antimicrobial stewardship-related peer-reviewed literature that detailed an "actionable" intervention for 2017. The top 13 publications were selected using a modified Delphi technique. These manuscripts were reviewed to highlight the "actionable" intervention used by antimicrobial stewardship programs to provide key stewardship literature for training and teaching and identify potential intervention opportunities within their institutions.

Objective: Use of ampicillin in outpatient parenteral antimicrobial therapy (OPAT) has historically been complicated by frequent dosing and limited stability. The purpose of this study was to evaluate stability of ampicillin using high-pressure liquid chromatography (HPLC) in an OPAT dosing model using continuous infusion at room temperature over 24 hours immediately following preparation compared with batches stored under refrigeration for 24 hours, 72 hours, and 7 days. Methods: An HPLC method was developed and validated as stability indicating using guidance in USP general Chapter <1225>. Four ampicillin batches were prepared for each experimental condition (immediate use and refrigerated storage for 24 hours, 72 hours, and 7 days). A pump was used to recirculate the solutions through medical-grade tubing for 24 hours. Triplicate 1-mL aliquots were removed from each batch at time 0, 4, 8, 12, and 24 hours and analyzed for ampicillin concentration. Results: Each batch was assayed for initial concentration (20.34-21.50 mg/mL), and percent recovery compared with that concentration thereafter. For the duration of infusion, the average recoveries were 96.4%, 95.8%, 94.6%, and 90.3% for immediate use, 24-hour storage, 72-hour storage, and 7-day storage, respectively. The recovery remained above 90% for all batches and time points, except for 7-day storage, which fell below 90% after 4 hours of circulation. Conclusion: Ampicillin can be prepared and stored in a refrigerator for up to 72 hours prior to continuously infusing at room temperature over 24 hours with less than a 10% loss of potency over the dosing period. This model supports twice weekly OPAT delivery of ampicillin.

No description available.

Given that neurocognitive impairment is a frequent complication of HIV-1 infection in Spanish-speaking adults, the limited number of studies assessing HIV-associated neurocognitive disorders (HAND) in this population raises serious clinical concern. In addition to being appropriately translated, instruments need to be modified, normed, and validated accordingly. The purpose of the current study was to examine the diagnostic utility of the HIV Dementia Scale (HDS) and International HIV Dementia Scale (IHDS) to screen for HAND in Spanish-speaking adults living with HIV infection. Participants were classified as either HAND (N = 47) or No-HAND (N = 53) after completing a comprehensive neuropsychological evaluation. Receiver operating characteristic analyses found the HDS (AUC =.706) was more sensitive to detecting HAND than the IHDS (AUC =.600). Optimal cutoff scores were 9.5 for the HDS (PPV = 65.2%, NPV = 71.4%) and 9.0 for the IHDS (PPV = 59.4%, NPV = 59.1%). Canonical Correlation Analysis found the HDS converged with attention and executive functioning. Findings suggest that while the IHDS may not be an appropriate screening instrument with this population, the HDS retains sufficient statistical validity and clinical utility to screen for HAND in Spanish-speaking adults as a time-efficient and cost-effective measure in clinical settings with limited resources.

Acute inflammatory response is caused by the rapid recruitment of leukocytes, mainly neutrophils and monocytes, from blood to the tissue site. Diverse agents, including invading pathogens, injured or dead cells, and other irritants, may stimulate this response. In the ensuing inflammatory response, the recruited leukocytes and their secreted molecules help in eliminating or containing the injurious agents and promoting tissue regeneration. But often this response is imprecise and can lead to bystander tissue damage. Unchecked neutrophil activation is implicated in the pathology of many inflammatory conditions. An in-depth understanding of the pathways regulating this response, therefore, becomes critical in identifying therapeutic targets for these diseases. In this study, we investigate the role of intestinal commensal bacteria in regulating the acute inflammatory response. Furthermore, we examine the mechanism by which Interleukin-1 (IL-1) controls the inflammatory response to sterile agents. Inflammatory responses have been studied in the context of host defense against pathogens. However, we report that the innate immune system needs to be primed by intestinal flora to enable neutrophil recruitment to diverse microbial or sterile inflammatory signals. This priming requires myeloid differentiation primary response gene (88) (MyD88) signaling. In antibiotic-treated mice, which have depleted intestinal flora, we show that neutrophils get released into the blood from the bone marrow, but have a specific defect in migration into the inflammed tissue. This deficiency can be restored by pre-stimulating the mice with a purified MyD88 ligand. Despite having reduced number of infiltrating neutrophils, antibiotic-treated mice make higher levels of pro-inflammatory cytokines in the tissue, after inflammatory challenge. This suggests that antibiotic-treated mice produce some anti-inflammatory molecule(s) that counteract the effect of the pro-inflammatory cytokines. However, this effect is not due to the overproduction of the anti-inflammatory cytokine, Interleukin-10 (IL-10). In summary, our findings highlight the role of commensals in the development of acute inflammatory responses to microbial and sterile particles. The inflammatory response to sterile dead cells has been shown to be critically dependent upon IL-1. However, several key aspects of the IL-1 signaling cascade including the source of IL-1 and the cellular target of IL-1 were unresolved. We find that in most cases, the injured cells are not a major contributor of IL-1 that is required to propagate the inflammatory signal. On the contrary, we demonstrate that both the isoforms of IL-1, IL-1α/IL-1β are generated by bone marrow-derived, tissue-resident responding cells, upon sensing the injury. We also sought to determine the identity of the cellular target of IL-1 signaling. Previous studies have shown that for cell death-induced neutrophil recruitment, interleukin-1 receptor (IL-1R) expression is required on parenchymal cells. To identify this parenchymal cell, we are currently in the process of making the conditional knockout mouse of IL-1R. The latter would facilitate the parenchymal tissue-specific deletion of IL-1R. In summary, this study reports our progress in unraveling key aspects of IL-1 signaling during sterile inflammation. Taken together, we have identified key modulators of the acute inflammatory response and their mechanisms of regulation. These findings would facilitate the development of new therapies for inflammatory diseases triggered by both microbe and sterile agents.

Mycobacterium tuberculosis infection is one of the leading causes of mortality worldwide. One third of the population is estimated to be infected, however only 5-10% of those individuals can transmit the disease. While T cell immunity initially limits mycobacterium growth, it is unclear why T cell immunity fails to sterilize the infection and prevent subsequent recrudescence. One hypothesis is T cell exhaustion is mediating the failure of T cell immunity late during infection. Here we show the development of T cell exhaustion during chronic infection, and that the inhibitory receptor T cell-immunoglobulin and mucin domain containing 3 (TIM3) mediates the development of T cell exhaustion. TIM3 accumulates on the surface of T cells throughout the course of infection and there is a subsequent decrease in effector cytokine production, such as IL-2, TNFα, and IFNγ. Furthermore, antibody blockade of TIM3 restores T cell function and improves bacterial control. Our results show that TIM3 is mediating T cell exhaustion during chronic TB infection and leading to suboptimal bacterial control.

Within East African countries many of the known infectious diseases of animals occur commonly and are poorly controlled. Foot-and-mouth disease (FMD) is one of the contagious viral diseases that has great impact on economic development both in terms of direct and indirect losses. The epidemiology of the disease is complex due to the presence of six of the seven serotypes and the presence of large numbers of both wild and domestic susceptible animals in the region. Decision-making to determine the importance of FMD control relative to the economic consequences and what FMD control strategies should be applied based on the epidemiological information is required. In this regard the first step is to investigate the genetic relationships/variability of East African isolates and their phylogeographic distribution. These can provide base-line information for designing control strategies by vaccination as well as the determination of the sources of infection. Sufficient genetic information on the FMO serotypes O, SAT-1 and SAT-2 are lacking and therefore the number of viral Iineages and genotypes or topotypes from East African countries could not be determined. Published studies on the relative occurrence and genotype distribution of FMO are largely confined to the southern and western part of the continent. In this study, the genetic profile of the 3 most prevalent serotypes (0, SAT-2 and SAT-1) recovered from outbreaks in East Africa between 1957 and 2003 was addressed. Phylogenetic analysis of partial and complete sequences of the 10 gene revealed the presence of distinct lineages and genotypes for East Africa as well as historical relationships of some of the genotypes with isolates from other regions. A great variation in the occurrence and distribution of these serotypes were found. All the African and the Middle East/South East Asian isolates of serotype O included in this study clustered into one lineage having 8 distinct topotypes. These results indicated that between countries as well as inter-regional (east and west Africa) spread of viruses occurred in the past. Inter-regional spread of the virus between eastern Africa and western Africa was also confirmed for SAT-1 viruses. The fact that phylogenetic links are found with both serotypes implies that the spread of viruses was possibly associated with unrestricted animal movement due to nomadic movement in Africa. The phylogenetic relationships of SAT-1 viruses are more diversified in Africa. Eight lineages and 11 genotypes were identified when the optimal nucleotide sequence differences of ≥ 23% for lineages and ≥ 6% for genotypes were used as a cut-off values. It was observed that viruses from Uganda are evolving independently from viruses elsewhere on the continent and clustered into 3 discrete lineages. In contrast, viruses from countries neighbouring Uganda, Kenya and Tanzania, clustered into one lineage. Uganda also harboured 3 topotypes of SAT-2 virus isolates, one is distinct for Uganda and the other are shared with Kenya and Zaire (DRC). This study highlighted distinct lineages found in Uganda and needs further investigation. Within SAT-2, 67 isolates from 22 African countries and Saudi Arabia clustered into 5 lineages which consisted of 15 genotypes. Clustering of viruses into distinct genotypes (topotypes) according to year of isolation and geographical origin was observed showing countries with common boundaries shared common epizootics in the past. These results also showed a link between eastern and southern African countries. Attempts were also made to investigate the incidence of FMD in Ethiopia using sera collected from cattle, small ruminants and wildlife. The results obtained from the liquid phase blocking ELISA and the 3ABC ELISA indicated the presence of SAT-1 and SAT-2 in buffalo populations in the southern part of Ethiopia while results from small ruminants and other wildlife were not indicative of any significant role in the epidemiology of FMD. Serological results also indicated that SAT-1 is present in cattle, although this serotype has not been previously identified. The cumulative molecular epidemiological results from this and previous studies indicated that genetic variability of FMD viruses can be independently maintained within country/countries or regions as well as inter-regions of Africa. The serological results from buffaloes in East Africa are also suggestive of a possible reservoir of the SAT types FMD in the region which has a great impact on the control of the disease. Furthermore, the numerous lineages and genotypes of FMD virus isolates in Africa having distinct or overlapping distributions as well as the genetic linkage between regions will complicate the epidemiology of the disease. Therefore, it is strategically important to consider a regional approach and the use of a vaccine which contains a cocktails of antigens of FMD virus strains. / Thesis (PhD)--University of Pretoria, 2004. / Veterinary Tropical Diseases / unrestricted

Includes bibliographical references / Introduction: Tuberculosis (TB) notification in South Africa has increased six fold over the last two decades mainly because of the Human Immunodeficiency Virus (HIV) epidemic. Globally, it was estimated that 73% of the TB cases were co-infected with HIV with more than 25% of this global co-infection burden being in South Africa alone. In 2012, globally 1.3 million deaths occurred due to TB; moreover 0.3 million were HIV-associated TB death. In 2010 TB was the leading cause of natural deaths in the population aged 15 to 24 years accounting for 14% of the total deaths in South Africa. In 2013 the proportion of patients with TB who were co-infected with HIV was extremely high at 62%.The outcome of co-infected patients was poorer than the outcome of HIV negative TB patients. However, there is little information available on the risk factors associated with TB treatment outcomes and the influence of co-infection. Method: A cross sectional study analysed Electronic TB Register (ETR.net) data from the Metro East Geographic Service Area (GSA) of the Cape Town Metro district. The dataset included adult patients aged 15 years or more, who initiated TB treatment between 1st July 2011 and 30th June 2012. In the descriptive analysis we analysed death separately but for the regression we merged death with unfavourable treatment outcome. Relative risks were used for measures of association. Univariate and multivariate analyses were performed using a generalized linear regression model. Statistically significant variables in the univariate analysis were included in the multivariate analysis. Findings: TB case notification in Eastern GSA was 922 per 100 000 population. Of the 12672 TB patients registered, 50% were co-infected with HIV. The incidence of death in co-infected was 5% versus 3% in uninfected, treatment success 67% versus 73% and unfavourable treatment outcome 28% versus 24%. The Khayelitsha sub-district had the highest proportion of the TB burden (37%) and of co-infection (65%). Fourteen percent of patients had extra-pulmonary TB (EPTB), 66% of whom were co-infected with HIV. In the multivariate analysis HIV (RR 1.2), retreatment (RR 1.4) and sputum smear microscopy not done (RR 1.4) were significantly associated with unfavourable treatment outcome. The sub districts Eastern (RR 0.9) and Northern (RR 0.7) were less likely to develop unfavourable outcome compared to Khayelitsha. In the stratified analysis, retreatment (RR 1.3) and smear not done (RR 1.3) were significant risk factors for an unfavourable treatment outcome in co-infected patients. Amongst HIV negative patients retreatment (RR 1.6) and smear not done (RR 1.6) were significant risk factors for an unfavourable treatment outcome. Conclusions: The incidence of TB is extremely high in the Eastern GSA of Cape Town however the prevalence of co-infection varies across the sub-districts. Although treatment outcomes have been improving, co-infection, retreatment and smear microscopy not done pre-treatment were factors significantly associated with an unfavourable treatment outcome. Eastern and Northern sub-districts were significantly more likely to have favourable treatment outcomes compared to Khayelitsha, where both TB incidence and HIV co-infection were greatest.