Mycobacterium tuberculosis complex (MTBC) is a causative agent of tuberculosis (TB) in humans and animals. The burden of tuberculosis in South Africa is worsened by the concurrent epidemic of HIV. The dynamic of TB epidemics has been investigated and yet little data has been given about the Eastern Cape, particularly Port Elizabeth. The study aimed to investigate the prevalence of drug resistant MTBC and to determine the mutations causing resistance in Port Elizabeth. One hundred and ninety (190) DNA samples isolated from sputum specimen in humans suspected of having TB were amplified using the Seeplex® MTB Nested ACE detection assay. To differentiate Mycobacterium tuberculosis complex (MTBC) members for surveillance purposes a multiplex polymerase chain reaction (PCR) method was done based on genomic regions of differences such as RD1, RD1mic, RD2seal, RD4, RD9 and RD12. Target genes known to confer resistance to first and second-line drugs were amplified and the amplicons sequenced using Big Dye Terminator DNA sequencing kit v3.1 (Applied Biosystems, UK). The patient’s demographic profiles were obtained from the National Health Laboratory Service (NHLS). All hundred and ninety DNA samples tested positive for MTBC using the Seeplex® MTB Nested ACE assay. Results show a high prevalence of extensive drug resistant TB in Port Elizabeth, Eastern Cape Province. One hundred and eighty four (184) DNA isolates were used in the identification of different MTBC species. We ended up working with 184 DNA isolates because we ran out of DNA, and we could not go back to isolate DNA from the affected individuals due to the fact that some patients died, while some have been released to go to their homes. From the 184 DNA isolates 45 (24.5%) isolates were identified to be M. tuberculosis, 94 isolates (51.1%) to be M. bovis BCG and 3 isolates (1.6%) to be M. cannetti. Sequencing results show the position of mutation in each DNA isolate; however in the study we got resistance to MDR to be 100% and 42% pre-XDR while 58% was XDR. These results raise an alarm for the prevalence MDR in MTBC from Port Elizabeth. This is a serious health concern which calls for a need to strategise on the identification of extensive drug resistant TB patients from multi-drug resistant TB patients and ensure monitoring of their treatment.

[No abstract available] / Science, Faculty of / Botany, Department of / Zoology, Department of / Graduate

Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills 1.6 million people worldwide every year, and there is an urgent need for targeting host-pathogen interactions as a strategy to reduce mycobacterial resistance to current antimicrobials. Non-coding RNAs are emerging as important regulators of numerous biological processes and avenues for exploitation in host-directed therapeutics. Although long non-coding RNAs (lncRNAs) are abundantly expressed in immune cells, their functional role in gene regulation and bacterial infections remains under-studied. Here, we identify an immunoregulatory, lincRNA-MIR99AHG, which is upregulated in macrophages upon IL-4/IL-13 stimulation and downregulated after Mtb infection and in active TB patients. To evaluate the functional role of lincRNA-MIR99AHG, we employed antisense GapmeR-mediated lncRNA knockdown experiments. Knockdown of lincRNA-MIR99AHG with LNA-GapmeRs significantly reduced intracellular Mtb growth in mouse and human macrophages and reduced proinflammatory cytokine production. In addition, in vivo treatment with MIR99AHG LNA-GapmeRs reduced the mycobacterial burden in the lung and spleen. In vivo LNA-GapmeR treatment experiments demonstrated a role of lincRNA-MIR99AHG as a regulator of macrophage polarization and a host-mediated response post Mtb infection. Further, lincRNA-MIR99AHG translocated to the nucleus and interacts with a high affinity to hnRNPA2/B1 following IL-4/IL-13 stimulation and Mtb infection. Together, these findings identify lincRNA-MIR99AHG as a positive regulator of inflammation to promote Mtb growth and a possible for host-directed targeting or for adjunctive therapeutics against TB.

STUDY OBJECTIVES: An analysis of IgG subclasses and allotypes in children with pulmonary Tuberculosis (PTB) in the Western Cape. DESIGN: Consecutive children under 15 years of age with microbiological proven PTB over an 8 month period- November 1993 to July 1994. SETTING: Teaching Hospitals in Cape Town. PATIENTS: Thirty-five cases were selected from 99 consecutive cases that were Mycobacterium tuberculosis positive, 15 of which were of Mixed and 20 were of Black Ancestry. CONTROL GROUP: Sera were selected from 224 Black Ancestry (59 children and 165 adults) and 211 Mixed Ancestry (67 children and 144 adults) that had no evidence for active tuberculosis or a history of previous TB diagnosis. MEASUREMENTS AND RESULTS: IgG subclasses, total IgG,and five allotypes: Glm(a), Glm(f), G2m(n), G3m(bl), G3m(gl) were determined by ELISA techniques. In the Mixed ancestry group the Glm(f) (p= 0.01), G2m(n) (p= 0.04) and G3m(gl) (p=0.001) allotypes were less frequently found in children with proven PTB. In the Black Ancestry subjects the G3m(g 1) allotype was significantly less common than in the control group (p < 0.001). CONCLUSIONS: Because allotypes are inherited in a Mendelian fashion, the observed association of childhood PTB and certain allotypes strengthens the hypothesis that a genetic susceptibility exists to acquiring TB.

Submitted to the Department of Epidemiology and Biostatistics, School of Public Health, University of Witwatersrand, in partial fulfillment of the requirements for the degree of Master of Science Epidemiology and Biostatistics, 2012 / TB is a high burden disease (prevalence: 940/100,000 in 2006) with high morbidity and mortality in South Africa and the primary health care facilities are well position to provide primary TB care in accordance to the national TB control guidelines and achieve desired treatment outcome targets. This study followed the TB management at Thandukukhanya clinic from 2000-2005 and found among others that the number of TB cases tripled, the TB cure rate progressively declined and DOTS support dwindle over the six years. The study was motivated by 26% decline in TB cure rate at Mkhondo sub-district from 2003 – 2005 and 76% increase in TB default in the same period. The TB cure rate in 2005 was 37% compared to 85% national target. The poor treatment outcome prevails despite availability of DOTS support in the program. In addition, the number of drug resistant TB has increased in the past years and extremely drug resistant TB emerged in the past three years in South Africa

Submitted in partial fulfillment of the requirements for the degree of Master of Science (Child Health) in the Department of Paediatrics, University of the Witwatersrand, Gauteng, South Africa, 2017 / Background: The incidence and morbidity of childhood tuberculosis (TB) in South Africa is high. Objectives: We evaluated the incidence of childhood TB in a regional hospital, the proportion of cases with a delayed diagnosis, and the determinants and outcomes thereof. Method: We conducted a retrospective cross-sectional review of hospital records of paediatric cases that were diagnosed with probable or confirmed TB at Addington Hospital, eThekwini, KwaZulu-Natal (KZN) from July through December 2013. Caregiver delays in diagnosis were based on history taking atinitial presentation, while health care worker or systems delays were calculated fromthe time from first presentation to diagnosis.Healthcare worker and health system delays were classified asbeing of 2-4 weeks and >4 weeksduration. Delays related to health policy implementation were also determined. Results: Fifty nine (74%) of the 80 children who werediagnosed with TBhad their recordsretrieved.The overall childhood TB incidence for Addington Hospital during the study period was 2.5%. Caregiver-related factors impacting on delay in TB diagnosis were observed in 25 (42%) of the 59 cases.Nineteen (32%)childrenhad a delay from initial presentation to TB diagnosis related to healthcare worker and health systems issues.Airway reactivity occurred more frequently in the group ofchildren who had a delay in diagnosis of>4 weeks (8/11, 73%)as compared to the non-delayed group (15/40, 38%), P=0.038. Conclusion: The diagnosis of TB in childrenis delayed in a substantial proportion of children. Significant improvements in healthcare that is provided to these childrenare required to avoid missed opportunities for diagnosis and treatment. / XL2018

No description available.

The role of the transposable insertion sequence IS<i>6110 </i>was studied in the evolution of <i>Mycobacterium tuberculosis </i>in 202 isolates from 40 countries. The isolates were analyzed by IS<i>6110 </i>insertion site mapping, spoligotyping, IS<i>6110 </i>RFLP fingerprints and <i>in silico </i>comparisons. Different IS<i>6110 </i>insertion sites exhibited a wide range of variation in the presence or absence of IS<i>6110 </i>in isolates varying between sites with only one isolate identified with the insertion, singletons, to sites where many isolates harboured an IS<i>6110 </i>insertion, common insertions.  95% of isolates were split into ten IS<i>6110 </i>cluster groups or lineages (ICG-1 to 8, ICG-a and ICG-b) based on their common IS<i>6110</i> insertion site patterns.  No <i>M. tuberculosis </i>isolates were found which were intermediate between ICG cluster groups.  A non-random association of IS<i>6110 </i>alleles over loci and also a high correlation between the common IS<i>6110 </i>cluster groups and spoligotype families suggested that common IS<i>6110 </i>insertions are predominantly the result of unique evolutionary event polymorphisms and they are therefore robust and valuable markers for phylogenetic and evolutionary studies of <i>M. tuberculosis.</i> 14 IS<i>6110-</i>assocaited deletions, including nine new regions of deletion were detected in the studied isolates.  Phylogenetic analysis of these genomic deletions demonstrated that they can also be used to classify the majority of MTB lineages including ICG-1/Beijing, ICG-3/CAS, ICG-5/a part of T, ICG-4/S and a major part of the ICG-6/LAM lineage. Published literature and DNA sequence databases were used to establish a global IS<i>6110 </i>database comprising of 524 different IS<i>6110</i> insertion sites across the genome and this database was used to study the role of IS<i>6110</i> in the fitness of <i>M. tuberculosis.  </i>The distribution of these sites showed a significant bias into intergenic regions, non-essential genes, multi-copy genes, other insertion elements and genomic repeat regions.  Common IS<i>6110</i> insertions may well have played an important role in the evolution of <i>M. tuberculosis.</i>

El presente estudio tiene como objetivos: Establecer la relación que existe entre el nivel de conocimientos, las prácticas sobre alimentación y el estado nutricional de los pacientes con tuberculosis del centro de salud José Carlos Mariátegui; identificar el nivel de conocimientos sobre alimentación de los pacientes con tuberculosis, identificar las prácticas sobre alimentación de los pacientes con tuberculosis; valorar el estado nutricional de los pacientes con tuberculosis; establecer la relación existente entre el nivel de conocimientos y las prácticas sobre alimentación de los pacientes con tuberculosis; establecer la relación existente entre las prácticas sobre alimentación y el estado nutricional de los pacientes con tuberculosis; siendo las hipótesis: El nivel de conocimientos se relaciona directamente con las prácticas sobre alimentación de los pacientes con tuberculosis; las prácticas sobre alimentación se relacionan directamente con el estado nutricional de los pacientes con tuberculosis. / --- The present study has as objectives: To establish the relationship that exists among the level of knowledge, practices on feeding and the nutritional state of the patients with tuberculosis of the center of health José Carlos Mariátegui; to identify the level of knowledge has more than enough the patients' feeding with tuberculosis, to identify the practices on the patients' feeding with tuberculosis; to value the nutritional state of the patients with tuberculosis; to establish the existent relationship between the level of knowledge and the practices on the patients' feeding with tuberculosis; to establish the existent relationship among the practices on feeding and the nutritional state of the patients with tuberculosis; being the hypotheses: The level of knowledge is related directly with the practices on the patients' feeding with tuberculosis; the practices on feeding are related directly with the nutritional state of the patients with tuberculosis.

La tuberculosis es una enfermedad infectocontagiosa de alta incidencia y prevalencia que produce además de trastornos físicos, serias repercusiones en la esfera psicoemocional, el cual se ve reflejado con mayor frecuencia en su autoestima, en tal sentido el presente estudio tuvo como objetivo determinar el nivel de autoestima de los pacientes del programa de control de tuberculosis del centro de salud Laura Rodríguez Dulanto-Duksil 2004. El método que se utilizó fue el descriptivo exploratorio, de corte transversal. La población estuvo conformada por los pacientes del Programa de Control de Tuberculosis del Centro de Salud Laura Rodríguez Dulanto – Duksil, conformado por 21 pacientes. La técnica que se utilizó fue la encuesta y el instrumento fue un formulario tipo cuestionario y el test de Autoestima de Cirilo Toro Vargas. Las conclusiones fueron; que el 56% de los pacientes tienen un nivel de autoestima alta positiva referido a las dimensiones cognitivas, afectivas y ética y 44% con autoestima baja positiva, autoestima alta negativa y autoestima baja negativa, que esta dado por alteraciones en las dimensiones física y social. En cuanto al nivel de autoestima en la dimensión física, el 67% presentan autoestima baja positiva y 33% una autoestima alta positiva. Respecto a la dimensión cognoscitiva 55% tienen autoestima alta positiva y 45% autoestima baja positiva. Acerca de la dimensión afectiva, 71% tienen autoestima alta positiva y 29% autoestima baja positiva. En relación a la dimensión social, 57% tienen autoestima baja positiva y 43% autoestima alta positiva. Sobre la dimensión ética, 81% tiene autoestima alta positiva y 19% autoestima baja positiva y autoestima alta negativa.