Magister Public Health - MPH / Background: The irrational use of medicines, and increasingly antimicrobials, remains a key health problem in many developing countries including Zambia. Inappropriate, ineffective and inefficient use of medicines is common in health facilities at all levels. There are many factors influencing irrational prescribing and dispensing of antimicrobials including patients, prescribers, dispensers, the supply system (including industry influences), government regulations and medicines information and misinformation. Study aim: The aim of the study was to assess the rational use and availability of antimicrobials at primary level health facilities under the Lusaka district community health office, Zambia. Study design: The study was a cross-sectional descriptive study, with prospective and retrospective components. A standardized research methodology, including tools and indicators, adapted from the World Health Organization, was employed. Study population and sampling: The study population included all the 30 government primary level health facilities (health centres) in Lusaka District, from which 20 primary health facilities were sampled using a combination of purposive and random sampling. Using the WHO standard indicators of rational drug use, this study assessed 800 patient encounters, 520 medicines inventory records, and other baseline data, from 20 health facilities at three different levels under the Lusaka district community health office, Zambia. Data collection: The data collection tools were numbered and labeled. Tool 1: Prescribing Indicator Form was used to collect prescribing data; Tool 2: Patient Care (Pharmacy) Form was used to record dispensing data; Tool 3: Antimicrobial Availability Form for recording data for the availability of the key indicator antimicrobials and their substitutes; Tool 4: Facility Indicator Consolidation Reporting Form was used for consolidating the data collected for each health facility under study; and Tool 5: Facility Medicines Use Indicator Consolidation Form was used for the consolidation of the drug use data for the entire study. Third year Pharmacy Technology students were trained for the data collection process. The patients were first observed from outside the prescriber's room and the dispensing area for consultation and dispensing times respectively, and then they were interviewed to collect the prescribing and dispensing data. The tools were pre-tested. Data analysis: After data checking and consolidation, quantitative data were categorized into continuous numerical variables. Calculations were done manually and using computerized analysis (Epi Info package) and presented as simple frequency and means. Ethics: Ethical clearance for the study was obtained from University of the Western Cape Senate Research Committee. Permission was obtained from the Lusaka Provincial and District health offices, being the authorities that are overseeing the health facilities included in the study. Furthermore, permission was obtained from the health centre in-charges. Consent was obtained from healthcare providers and patients. Key results and discussion: The study found that at the primary level facilities there were more Clinical Officers (55%) than Medical Doctors (25%) and Registered Nurses (20%) in charge of prescribing. The main dispensers were Pharmacy Technologists (85%); there were no Pharmacists available in any of the facilities. A third [259 (32.4 %)] of all the 800 patients in the study were children below 12 years of age. Across the clinics, a mean of 2.94 medicines were prescribed per prescription, with an extremely low rate of prescribing drugs by generic name (36.7%). The proportion of prescriptions including an antibiotic was 36.2 % and 3.4 % included an injectable drug. Linking the antimicrobials and injections to patient diagnoses indicated that many were probably irrational, prescribing decisions. Amoxicillin and metronidazole were by far the most commonly prescribed antimicrobials at 32.0 % and 17.2 % of total antimicrobials, respectively. The essential drugs list was available in 80.0% of facilities and a high percentage of medicines were prescribed from the essential medicines list (81.2%). The overall mean percentage of medicines packages correctly labeled was considerably low at 44.8 %. The average consultation time was short at 4.0 (range 1-8.4) minutes, whereas the dispensing times were equally short and averaged at 116.6 (range 15-360) seconds, with the range of 15 to 360 seconds. The average percentage of first line antimicrobials available at health facilities was 79 %; and the average percentage of second line, substitute, antimicrobials available was 15 %. Conclusion: In line with studies from other settings, this medicines use study found considerable overuse and irrational use of antimicrobials in the primary health care clinics in Lusaka District. Irrational medicine prescribing was common and poor dispensing practices were also seen, resulting in poor use of and adherence to medicines and, consequently, poor therapeutic outcomes. Recommendations: Several recommendations have been formulated. They include: Reinforcing the Drug Therapeutic Committees (DTCs) at the national and the local facility level to help manage medicines use; clarification of prescribers and dispensers roles and responsibilities; development, enforcement or adaption of standard operating procedures (SOPS) for prescribing and dispensing; and improvement of prescribing and dispensing practices through introduction of appropriate education, supervision and audit.

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Shigella spp. está entre as quatro bactérias mais isoladas de fezes diarreicas no Brasil. No mundo cerca de 164,7 milhões de casos de shigelose ocorrem anualmente, sendo a maioria em países em desenvolvimento. O gênero Shigella spp. possui quatro espécies, sendo Shigella sonnei e Shigella flexneri as espécies mais frequentemente isoladas no Brasil e no mundo. O monitoramento de linhagens resistentes de Shigella spp. é essencial, pois este garante uma terapia eficiente quando necessária. Especificamente, a maioria dos estudos realizados com linhagens de S. sonnei no país verificaram apenas a ocorrência dessa e há poucos estudos que investigaram o potencial patogênico e a diversidade genotípica dessa espécie. Os objetivos desse projeto foram analisar o potencial patogênico, o perfil de resistência a antimicrobianos e a diversidade genotípica de linhagens de S. sonnei isoladas durante três décadas no Estado de São Paulo. No total foram caracterizadas 72 linhagens de S. sonnei isoladas de humanos, entre os anos de 1983 a 2014, quanto à presença de 12 genes de virulência por PCR, perfil de suscetibilidade frente a 16 antimicrobianos por disco difusão e tipagem molecular por Pulsed-field gel electrophoresis (PFGE), Enterobacterial repetitve intergenic consensus PCR (ERIC-PCR), Multiple-locus variable-number tandem-repeat analysis (MLVA) e 20 linhagens tipadas por Multi-locus sequence typing (MLST). Todas as linhagens apresentaram os genes de virulência ipaH, iuc e sigA. O gene ipaBCD foi encontrado em 14 (19%) linhagens, os genes ial e virF em 13 (18%) linhagens e o gene sen em sete (10%) linhagens. Os genes set1A, set1B, pic, sat e sepA não foram detectados. As mais altas taxas de resistência foram frente à sulfametoxazol-trimetoprim encontrada em 42 (58,3%) linhagens e frente à tetraciclina encontrada em 30 (41,6%) linhagens. Onze (15,5%) linhagens foram resistentes à ampicilina e piperacilina. Três (4,2%) linhagens foram resistentes à cefotaxima. Três (4,2%) linhagens foram resistentes ao cloranfenicol. Duas (2,8%) linhagens foram resistentes à ampicilina-sulbactam. Duas (2,8%) linhagens foram resistentes ao ácido nalidíxico. Uma (1,4%) linhagem foi resistente à amoxicilina-ácido clavulânico. Cinco (7%) linhagens foram multidroga resistentes (MDR). O dendrograma gerado pelo PFGE agrupou as 72 linhagens de S. sonnei em dois clusters designados PFGE-A e PFGE-B. O cluster PFGE-A agrupou 39 linhagens isoladas entre 1983-2014 com uma similaridade >=73,6% e mais especificamente 35 dessas linhagens apresentaram uma similaridade >=80,3%. O cluster PFGE-B agrupou 33 linhagens de S. sonnei isoladas entre 1984-2014 com uma similaridade >=74,7% e 27 dessas linhagens exibiram uma similaridade >=83,0%. Similarmente, o dendrograma gerado pelo ERIC-PCR agrupou as 72 linhagens de S. sonnei em dois clusters designados ERIC-A e ERIC-B. O cluster ERIC-A agrupou 37 linhagens isoladas entre 1983-2014 que exibiram uma similaridade >=78,8% e mais especificamente 36 dessas linhagens apresentaram uma similaridade >=82,3%. O cluster ERIC-B agrupou 34 linhagens de S. sonnei isoladas entre 1987-2014 que exibiram uma similaridade >=84,0%. Também por MLVA as linhagens foram agrupadas em dois clusters designados MLVA-A e MLVA-B. O cluster MLVA-A agrupou 31 linhagens isoladas entre 1983-2014 com uma similaridade >=40%. O cluster MLVA-B agrupou 41 linhagens isoladas entre 1983-2014 com uma similaridade >=21,6%. Todas as 20 S. sonnei foram tipadas por MLST como ST152. Conclui-se que o potencial patogênico das linhagens estudadas foi destacado pela presença de importantes genes de virulência. A alta porcentagem de resistência para alguns antimicrobianos testados, tais como, sulfametoxazol-trimetoprim e tetraciclina é preocupante e pode levar à falha terapêutica. Os resultados da tipagem molecular sugerem que existam dois subtipos prevalentes nas linhagens de S. sonnei estudadas que se diferenciaram pouco geneticamente e contaminaram humanos durante 31 anos na região metropolitana de Ribeirão Preto no Estado de São Paulo. O resultado do MLST indica que as linhagens estudadas de Shigella sonnei isoladas no Brasil descendem de um precursor comum / Shigella spp. is among the four most isolated bacteria from diarrheal faeces in Brazil. In the world about 164.7 million cases of shigellosis occur annually, mostly in developing countries. The genus Shigella spp. comprises four species, being Shigella sonnei and Shigella flexneri the most frequently isolated species in Brazil and worldwide. The monitoring of resistant strains of Shigella spp. is essential and ensures an effective therapy when necessary. Specifically, the majority of the studies with S. sonnei performed in the country verified only the occurrence of this bacterium and there are few studies that investigated the pathogenic potential and genotypic diversity of this species. The aims of this project were to analyze the pathogenic potential, antimicrobial resistance profile and genotypic diversity of S. sonnei strains isolated during three decades in the State of São Paulo. In total, 72 of S. sonnei strains isolated from humans, between the years 1983-2014, were characterized for the presence of 12 virulence genes by PCR, resistance profile against 16 antimicrobials by disk diffusion and molecular typing by Pulsed-field gel electrophoresis (PFGE), Enterobacterial repetitve intergenic consensus PCR (ERIC-PCR), Multiple-locus variable-number tandem-repeat analysis (MLVA) and 20 strains typed by Multi-locus sequence typing (MLST). All the strains contained the ipaH, iuc and sigA genes. The ipaBCD gene was detected in 14 (19%) strains, the ial and virF genes in 13 (18%) strains and the sen gene in seven (10%) strains. The set1A, set1B, pic, sepA and sat genes were not detected. The highest resistance rates were against trimethoprim-sulfamethoxazole found in 42 (58.3%) strains and against tetracycline found in 30 (41.6%) strains. Eleven (15.5%) strains were resistant to ampicillin and piperacillin. Three (4.2%) strains were resistant to cefotaxime. Three (4.2%) strains were resistant to chloramphenicol. Two (2.8%) strains were resistant to ampicillin-sulbactam. Two (2.8%) strains were resistant to nalidixic acid. One (1.4%) strain was resistant to amoxicillin-clavulanic acid. Five (7%) strains were multidrug resistant (MDR). The dendrogram generated by PFGE grouped the 72 S. sonnei strains into two clusters designated PFGE-A and PFGE-B. The PFGE-A cluster comprised, 39 S. sonnei strains isolated between 1983 and 2014 with a similarity above 73.6% and more specifically 35 of those strains exhibited a similarity >= 80.3%. The PFGE-B cluster grouped, 33 S. sonnei strains isolated between 1984 and 2014 with a similarity above 74.7%, and 27 of those strains exhibited a similarity above 83.0.Similarly, the dendrogram generated by ERIC-PCR grouped the 72 S. sonnei strains into two clusters designated ERIC-A and ERIC-B. The ERIC-A cluster comprised, 37 S. sonnei strains isolated between 1983 and 2014 that exhibited a similarity above 78.8% and specifically 36 strains of those exhibited a similarity >= 82.3%. The ERIC-B cluster grouped, 34 S. sonnei strains isolated between 1987 and 2014 that exhibited a similarity above 84.0%. Also, by MLVA strains were grouped into two clusters designated MLVA-A and MLVA-B. The MLVA-A cluster comprised 31 strains isolated between 1983 and 2014 with a similarity >=40%. The MLVA-B cluster comprised 41 strains isolated between 1983 and 2014 with a similarity >=21.6%. All the 20 S. sonnei were typed by MLST as ST152. In conclusion, the possible pathogenic potential of the strains studied was highlighted by the presence of important virulence genes. The high percentage of resistance to some of the antimicrobials tested such as trimethoprim-sulfamethoxazole and tetracycline is worrying and may lead to therapeutic failure. Molecular typing results may suggest that there are two prevalent subtypes of S. sonnei strains studied that differed little genetically and have been contaminating humans over 31 years in the metropolitan region of Ribeirão Preto in the São Paulo State in Brazil. The result of MLST indicates that the Shigella sonnei strains studied isolated in Brazil descended from a common precursor