Tuberculosis (TB) is the most common opportunistic infection in HIV-infected patients and the emergence of drug-resistant tuberculosis (DR-TB) is a growing problem in resource-limited settings (RLS). TB diagnosis in most RLS still depends on smear microscopy for acid-fast bacilli (AFB) while adequate infrastructure for testing drug sensitivity is unavailable. However, molecular diagnostics that detect Mycobacterium tuberculosis (Mtb) DNA and its genetic markers of drug resistance were recently developed. In this thesis I describe the use of a molecular diagnostic, Genotype MTBDRplus, for characterizing DR-TB and patterns of tuberculosis-like infection in two cities in south-west and north-central Nigeria. I found high rates of DR-TB in Nigerian HIV-infected individuals (9.3% for RIF or INH) with significantly different amounts by location (18.18% in south-west vs. 3.91% in north-central Nigeria, p=0.01). RIF resistance, indicative of MDR-TB, was found in 5.52% treatment-naïve patients, far exceeding the WHO predictions (0-4.3%). Furthermore, RIF resistance was genetically distinct, suggesting location-specific transmission of drug resistance (p=0.04). Genotype MTBDRplus correctly identified the drug-resistant samples compared to sequencing in 96.8% of cases. Mtb was confirmed in 56% of patients and was less likely to be found in patients on ART, while controlling for other relevant demographic characteristics (OR 0.29, P=0.02). Only abnormal respiratory findings on auscultation and the direct sputum smear grade greater than 3/100 were significant predictors of Mtb infection (OR 3.28, P=0.03; OR 6.40, p<0.01 respectively). Concentrated sputum smear was not significantly correlated with Mtb infection, except at the highest grades (>2+). Furthermore, in 49% of samples that were not confirmed for Mtb other actinomycetes were found: atypical Mycobacteria (ATM), Rhodococcus spp., Nocardia spp., Corynebacterium spp. I conclude that concentrated sputum AFB smears may misidentify bacteria as Mtb in a subset of HIV-infected patients. These individuals may have a different, even uncharacterized, actinomycete infection in the respiratory tract. Furthermore, total DR-TB in HIV-infection is high and transmission of DR-TB in HIV-infected patients in Nigeria is higher than estimated by the WHO. Molecular diagnostics are a rapid method for identifying Mtb and monitoring DR-TB, and can guide appropriate treatment decisions for respiratory infections in RLS with a high HIV burden.

Tuberculosis (TB) is an airborne infection. Though effective anti-TB drugs have been available for more than 50 years, over one-third of the world’s population is exposed to TB bacterium; deaths due to TB infection occur at high frequency every day worldwide. Today, drug-resistant TB, TB/HIV co-morbidity and poor health infrastructure are major challenges worldwide, particularly in less developed countries. The primary objective of the study was to assess the progress of TB control programs in twenty-two Eastern Mediterranean Region countries toward Millennium Development Goals (MDGs) including implementation of the Directly Observed Treatment, Short-course (DOTS). Also, the study was designed to explore TB/HIV co-morbidity and to assess some factors potentially associated with TB progress in the region. Secondary data, obtained from the World Health Organization, World Bank, and World Resource Institute on line databases were used. Paired samples t-test and bivariate correlation were conducted. Between 1990 and 2005, TB incidence had decreased 9%, TB prevalence had decreased 37% (statistically significant) and TB mortality had decreased 28%; nevertheless, MDG targets were not met. TB/HIV co-morbidity increased in the region especially in HIV-high burden countries. Though DOTS population coverage was increased to 94% in 2005, DOTS new smear-positive case detection rate was 61% (target 70%) and DOTS treatment success was 80% (target 85%). Thus, the 1991 Stop TB Partnership targets were not met. In spite of the progress of TB control programs in the EMR, MDGs and DOTs targets of 2005 were not obtained. Further efforts such as allocation of more resources, strengthening of TB surveillance systems, extension of drug-resistant TB and TB/HIV collaborative programs, and TB research are required to achieve MDGs by 2015 and to fully implement the new Stop TB Strategy in the region.

p. 1-71 / Submitted by Santiago Fabio (fabio.ssantiago@hotmail.com) on 2013-04-11T19:25:20Z No. of bitstreams: 1 Dissertacao Carolina Carvalho MP.pdf: 827108 bytes, checksum: 8070a2b199b6cd79e684b870ff01497c (MD5) / Approved for entry into archive by Maria Creuza Silva(mariakreuza@yahoo.com.br) on 2013-04-11T19:28:07Z (GMT) No. of bitstreams: 1 Dissertacao Carolina Carvalho MP.pdf: 827108 bytes, checksum: 8070a2b199b6cd79e684b870ff01497c (MD5) / Made available in DSpace on 2013-04-11T19:28:07Z (GMT). No. of bitstreams: 1 Dissertacao Carolina Carvalho MP.pdf: 827108 bytes, checksum: 8070a2b199b6cd79e684b870ff01497c (MD5) Previous issue date: 2007 / A subnotificação da comorbidade tuberculose e Aids resulta no desconhecimento da dimensão da associação entre essas doenças. O conhecimento do status HIV e da presença de Aids dos pacientes com tuberculose é essencial para o ótimo manejo do paciente. No Brasil, a vigilância dos casos de tuberculose e Aids é realizada principalmente por meio do Sistema de Informação de Agravos de Notificação (Sinan). O pareamento dos bancos de dados informatizados desses agravos pode auxiliar na identificação da subnotifcação da comorbidade TB-Aids. Objetivo: Avaliar a subnotificação da comorbidade TB-Aids no Sinan TB, no Brasil, no período de 2000 a 2005. Metodologia: Estudo descritivo exploratório utilizando os registros de casos notificados no banco do Sinan TB e banco nacional da Aids. Foram considerados casos de comorbidade TB-Aids subnotificados no Sinan TB, os registros sem informação de presença desse agravo e que foram pareados a registros da Aids que possuíssem ano de diagnóstico de Aids igual ou anterior ao ano de notificação da TB, assim como os registros de um mesmo paciente cujos registros anteriores possuíssem essa informação. Os registros de TB que possuíam informação de presença de Aids em uma variável específica foram considerados casos de comorbidade TB-Aids reconhecidos. Resultados: A subnotificação da comorbidade TB-Aids identificada no Sinan TB foi de 17,7%. Essa porcentagem variou bastante entre estados. A incorporação dos registros subnotificados aos previamente reconhecidos elevou a proporção da comorbidade TB-Aids no Brasil de 6,9% para 8,4% no período analisado. Conclusões: A evidência de subnotificação da comorbidade TB-Aids no Brasil deve deflagrar modificações no sistema de vigilância desses agravos de modo a permitir que os programas nacionais disponham dessa informação. / Salvador

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-07-17T14:33:57Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação de Mestrado - Suelene Suassuna Silvestre Alencar.pdf: 1698152 bytes, checksum: 7bc449edbb1386a1875057dc6f3f376f (MD5) / Made available in DSpace on 2017-07-17T14:33:58Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) Dissertação de Mestrado - Suelene Suassuna Silvestre Alencar.pdf: 1698152 bytes, checksum: 7bc449edbb1386a1875057dc6f3f376f (MD5) Previous issue date: 2001-01-10 / Estudo realizado com o objetivo de avaliar a translocação bacteriana (TB) do trato gastrointestinal para órgãos viscerais em ratos submetidos à ligadura do ducto colédoco e submetidos à administração por via oral (gavagem) de E.coli marcada com 99mTecnécio (99mTc-E.coli). Quatro grupos de ratos foram estudados: grupo I (n=10) ligadura do colédoco, grupo II (n=10) controle ou “sham operation”, grupo III (n=12) ligadura do colédoco e gavagem com 99mTcE.coli e grupo IV (n=5) controle ou “sham operation”e gavagem com 99mTc-E.coli. Usando técnica asséptica e sob anestesia, os ratos foram submetidos à laparotomia. Nos ratos dos grupos I e III realizou-se ligadura do colédoco com fio de seda nº 3 zeros e nos ratos dos grupos II e IV apenas manipulação do colédoco com pinça de Adison (sham operation). Após sete dias de observação, os animais dos grupos I e II foram mortos e ressecados fígado, baço, linfonodos mesentéricos e pulmões para exame microbiológico (meios Agar-sangue e Agar Mac Conkey) e exame histopatológico (coloração H.E. e Tricrômico de Masson) por análise morfométrica. O nível de bilirrubina nos grupos ictéricos foi elevado em relação aos do grupo controle. A incidência de bactérias translocadas foi maior no grupo I comparada ao controle p 0,05. Nos animais dos grupos III e IV, após sete dias de observação, foi administrada por via oral (gavagem) 99mTcE.coli e após 24 Hs, os ratos de ambos os grupos foram mortos e seus órgãos retirados para contagem da radioatividade em cintilador gama. Os resultados não mostraram diferença estatisticamente significativa na captação da -E.coli entre os dois grupos (p 0,05). Porém a análise das interações grupo x órgão mostrou diferença entre os grupos ictérico e controle para os órgãos: fígado e pulmão. Os dados disponíveis permitem concluir que em ratos ictéricos por ligadura do colédoco ocorreu translocação de bactérias detectáveis por exame microbiológico. Não ocorreu translocação de bactérias com 99mTc no modelo proposto. / This study was designed to evaluate the bacterial translocation (TB) from the gastrointestinal tract to visceral organs in rats submitted to laparotomy and common bile duct ligation (CBDL). Four groups of rats were studied: group I (n = 10) CBDL; group II (n=10) control or “sham operation”; group III (n= 12) CBDL and 99mTc-E.coli and group IV (n=5) control or “sham operation” e 99mTc-E.coli. All the animals were operated with aseptic technic under intraperitoneal anesthesia with pentobarbital sodium (200mg/Kg). On 7th postoperative day the animals of groups I and II were killed with a letal dosis of anesthetic and the liver, spleen, mesenteric lynfonodes and lungs were ressecated to microbiological (Agar-blood and Agar-Mac Conkey) and histological examination (H.E. and Masson Trichromic) through morphometric analysis. On 7th postoperative day the animals of III and IV groups were submitted to 99mTc-E.coli gavage and after 24 hr they were killed and their organs were ressected. After that, the bacterial radioactivity was mensured through an Automatic count of Gama Radioative – model ANSR (Abott Laboratories). The bilirrubin levels of the jaundiced rats were elevated compared with the control groups. The incidence of bacterial translocation was higher in group I compared with control group (p 0,05). The results showed no significant differences among the jaundiced and control groups to the liver and lungs. The data allow to conclude that in jaundiced rat with ligated bile duct occurred bacterial translocation through microbiological analyses. The model proposed showed no bacterial translocation by the labeled 99mTc technic.

The goal of the graduation thesis is building of a working replica of the motorcycle engine Laurin&Klement, type TB from 1902. The thesis focuses on the manufacturing of cast parts. The piece production of the engine has been based on extant original pieces, missing pieces have been manufactured according to period photographs and leaflets. This method can be applied for production of missing or damaged pieces of historical motorcycles‘ engines.

HIV and Tuberculosis (TB) co-infection place an immense burden on health care systems as they act in synergy to worsen disease prognoses. TB is the most common cause of death in people living with HIV (PLWH) and in turn, HIV is the most significant risk factor for progressing from latent to active TB disease. While HIV and TB are endemic in sub-Saharan Africa, they also disproportionately affect marginalized populations in Canada. Unfortunately, the only licensed TB vaccine, BCG, does not protect from adult pulmonary TB and is not recommended for PLWH. Thus, the development of novel TB vaccines, which are safe and effective in PLWH, remains an urgent global necessity. We have found that humanized mice (hu-mice) are ideal models to research this as they can be successfully infected with HIV, TB and HIV/TB and recapitulate human disease pathology. A next-generation respiratory mucosal (RM) trivalent chimpanzee adenoviral-vectored vaccine (Tri:ChAd68) was developed and tested in our naïve and HIV-infected hu-mice. When immunizing naïve hu-mice, a trend of increased M.tb-specific CD4+ T cells producing IFNγ and TNFα in the lungs and spleen was observed. After subsequent M.tb infection, the vaccinated naïve hu-mice also exhibited significantly reduced lung mycobacterial burden, tissue dissemination and lung pathology. We then investigated the vaccine immunogenicity and ability to protect from TB in the context of HIV. Our immunized HIV-infected hu-mice were also able to produce M.tb-specific T cells and when challenged with M.tb, we observed a decreased trend in mycobacterial load in the lungs, indicating that the vaccine may be able to offer protection against TB when a prior HIV infection is present. These findings demonstrate the protective potential of the RM Tri:ChAd68 vaccine against TB disease for PLWH. In the future, we will test this vaccine in antiretroviral treated HIV-infected hu-mice to increase clinical significance. / Thesis / Master of Science in Medical Sciences (MSMS) / HIV and TB are major diseases that can occur together, severely worsening patients’ health and challenging global healthcare systems. The current TB vaccine, BCG, isn’t ideal for people living with HIV (PLWH), causing this vulnerable population to be at greater risk of getting TB infection. Therefore, developing a new TB vaccine that is safe and effective in PLWH is an urgent global issue. We used humanized mice that develop human immune cells to test a novel TB vaccine delivered to the lungs (Tri:ChAd68) to see if it could protect against TB and overcome immune challenges from HIV. We saw increased immune responses and lower TB infection in our vaccinated humanized mice and the vaccine appeared to also be beneficial in the mice that had prior HIV infection. This suggests the Tri:ChAd68 vaccine may be able to offer protection against TB in PLWH; however, more studies are needed to conclude this.

No description available.

Collaborative TB/HIV management is essential to prevent and treat TB among HIV-positive TB patients, and to ensure that HIV-positive TB patients are detected and treated appropriately. This quantitative, descriptive, contextual study identified problems encountered during the implementation of TB case detection among HIV-positive individuals in one Ethiopian hospital. During December 2012, 300 checklists were completed about HIV-positive patients’ TB/HIV collaborative management, as reflected in their files. Only 60.2% of HIV-positive patients, who should have received Isoniazid preventive treatment (IPT), were placed on this treatment. X-rays and laboratory examinations of sputum samples were not done according to the Ethiopian guidelines. Most TB patients’ initial screening was done by nurses, not doctors, and included only symptom screening without CD4 count considerations. Managers and healthcare personnel should improve IPT, especially for those with early HIV infection and timely effective treatment for those suffering from TB, before complications arise / Health Studies / Health Studies / M.A. (Public Health)

Collaborative TB/HIV management is essential to prevent and treat TB among HIV-positive TB patients, and to ensure that HIV-positive TB patients are detected and treated appropriately. This quantitative, descriptive, contextual study identified problems encountered during the implementation of TB case detection among HIV-positive individuals in one Ethiopian hospital. During December 2012, 300 checklists were completed about HIV-positive patients’ TB/HIV collaborative management, as reflected in their files. Only 60.2% of HIV-positive patients, who should have received Isoniazid preventive treatment (IPT), were placed on this treatment. X-rays and laboratory examinations of sputum samples were not done according to the Ethiopian guidelines. Most TB patients’ initial screening was done by nurses, not doctors, and included only symptom screening without CD4 count considerations. Managers and healthcare personnel should improve IPT, especially for those with early HIV infection and timely effective treatment for those suffering from TB, before complications arise / Health Studies / Health Studies / M.A. (Public Health)

Made available in DSpace on 2015-04-11T13:54:24Z (GMT). No. of bitstreams: 1 Marcia Alves de Souza.pdf: 1923965 bytes, checksum: 3ad1484efad384495579203b0e85259c (MD5) Previous issue date: 2013-05-30 / FAPEAM - Fundação de Amparo à Pesquisa do Estado do Amazonas / A Tuberculose (TB) é uma doença infecciosa causada pelo complexo Mycobacterium tuberculosis, sendo considerada um grave problema de saúde pública mundial. Atualmente, isolados de M. tuberculosis resistentes a pelo menos um medicamento utilizado no tratamento da TB tem sido documentados em todos os países. De acordo com a Organização Mundial de Saúde (OMS) a TB multirresistente (TBMR) é definida quando, isolados de M. tuberculosis de pacientes apresentam resistência a pelo menos Isoniazida e Rifampicina, os dois fármacos fundamentais no tratamento da TB. A resistência à Rifampicina tem sido associada às mutações gênicas no bacilo, no gene rpoB (referentes aos códons 531, 526 e 516). Para a Isoniazida, as mutações associadas à resistência têm sido relatadas nos genes katG, inhA, ahpC e kasA, sendo que a mutação no gene katG, referente ao códon 315, tem sido a mais citada para resistência a este fármaco. Neste contexto, métodos moleculares têm sido propostos pra detecção de mutações gênicas, em isolados de M. tuberculosis, que possam estar associadas à resistência aos fármacos. O presente estudo avaliou o desempenho da PCR multiplex alelo específico (PCR-MAS), diretamente em 86 amostras de escarro de pacientes com TB pulmonar multibacilares (n=42) e paucibacilares (n=44) da Policlínica Cardoso Fonte. A PCR-MAS teve como alvos: os genes katG ,inhA e rpoB. A concordância entre a PCR-MAS e o Método de Redução de Nitrato foi avaliada utilizando o teste kappa e a associação entre as mutações gênicas e a resistência fenotípica aos fármacos foi realizada pelo teste exato de Fisher. A análise de concordância, pelo teste kappa, foi realizada entre as PCR-MAS a partir de amostra de escarro e de isolados de M. tuberculosis. A PCR-MAS apresentou fraca concordância com o Método de Redução de Nitrato, pois de 18 amostras resistentes à Isoniazida, apenas em 4 (22,2%) foram detectadas as mutações para o gene katG ou inhA. No entanto, a avaliação da sensibilidade fenotípica à Rifampicina, apresentou boa concordância com a PCR-MAS (kappa = 0,7237), quando as amostras foram de pacientes de TB pulmonar multibacilar. Além disso, houve associação da presença de mutações no gene rpoB com resistência fenotípica à Rifampicina (p = 0.0014). Em relação a concordância entre as PCR-MAS, de amostras de escarro e seus respectivos isolados de M. tuberculosis, o desempenho foi excelente quando testados em amostras de pacientes com TB pulmonar multibacilar, para detecção de mutações no gene rpoB (kappa = 0,7742). Portanto, os resultados obtidos com a PCR-MAS, a partir de amostras de escarros, foram satisfatórios e poderão ser utilizados para monitorar e pesquisar as mutações associada à resistência à Rifampicina em pacientes de TB multibacilar na rede básica de saúde, pois é um teste rápido, reprodutível e de menor custo.