ABSTRACT In Fortaleza, the capital of Ceara State, Brazil, the detection rate of tuberculosis (TB) in 2018 was 65.5/100,000 inhabitants with a cure rate of 59.1%, which is higher than the country average. This study investigated the risk factors associated with drug-resistant tuberculosis (DR-TB) and identified the drug-resistance phenotype and resistance-conferring mutations. The geographic distribution of DR-TB in Fortaleza, Brazil, was also determined. From March 2017 to February 2018, 41 DR-TB isolates and 69 drug-susceptible pulmonary TB isolates were obtained from patients seen at a referral hospital in Fortaleza, Brazil. Samples were subjected to phenotypic and genetic analysis of resistance; the spatial distribution of the participants was also analyzed. Primary resistance was high (50.9%) among participants. The following risk factors for DR were identified: being female ( p = 0.03), having diabetes ( p < 0.01), history of previous TB disease ( p < 0.01), and the number of intra-domiciliary contacts ( p < 0.01). Analysis by multiplex allele-specific polymerase chain reaction detected mutations in the genes katG (65.8%) , rpoB (43.9%), inhA promoter (14.6%), and gyrA (9.8%). Sequencing identified mutations in the the genes katG (75.6%), inhA promoter (19.5%), rpoB (85.4%), and gyrA (100%). There was no mutation in the rrs gene. Spatial analysis showed DR-TB isolates distributed in areas of low socioeconomic status in the city of Fortaleza. Our results emphasized the importance of detecting resistance to TB drugs. The resistance found in the gene gyrA is of concern due to the high number of pre-extensive DR-TB cases in Fortaleza.

OBJECTIVE: The aim of this study is to investigate the presence of human papillomavirus DNA and genotypes in breast cancer and normal breast tissue samples obtained from women from the northeast region of Brazil. METHOD: One hundred three breast cancer samples and 95 normal breast samples, as the non-malignant controls, were studied. DNA extraction was verified by human beta-globin gene amplification, and polymerase chain reaction was conducted based on HPV L1-specific consensus primers MY09/MY11 and GP5+/GP6+, followed by nested multiplex polymerase chain reaction with type-specific primers for the E6/E7 consensus region. RESULTS: Human papillomavirus DNA was detected in 51 (49.5%) breast carcinoma samples and 15 (15.8%) normal breast samples (p<0.0001). Human papillomavirus genotypes 6 and 11 were identified in 15.2% of all samples. CONCLUSIONS: The high frequency of human papillomavirus infection in breast cancer samples indicates a potential role of this virus in breast carcinogenesis in the studied participants.

BACKGROUND The detection of live Mycobacterium leprae in soil and animals other than humans suggests that the environment plays a role in the transmission of leprosy. OBJECTIVE The objective of this study was to investigate the presence of viable M. leprae in natural water sources used by the local population in five municipalities in the state of Ceará, northeastern Brazil. METHODS Samples were collected from 30 different sources. Viable bacilli were identified by reverse transcriptase polymerase chain reaction (PCR) of the M. leprae gyrA gene and sequencing of the PCR products. Physicochemical properties of each water source were also assessed. FINDINGS M. leprae gyrA mRNA was found in 23 (76.7%) of the water sources. No association was found between depth of the water and sample positivity, nor was there any association between the type of water used by the population and sample positivity. An association between viable M. leprae and temperature and pH was found. Georeferencing showed a relation between the residences of leprosy cases and water source containing the bacterium. MAIN CONCLUSIONS The finding of viable M. leprae in natural water sources associated with human contact suggests that the environment plays an important role in maintaining endemic leprosy in the study region.

Abstract INTRODUCTION: This study quantified Mycobacterium leprae bacilli in environmental water samples from five municipalities in the State of Ceará by quantitative polymerase chain reaction (qPCR) and compared the identified genotypes with those obtained from leprosy patient biopsies. METHODS: We collected five replicas from each of the 30 selected reservoirs and skin lesion biopsies from 25 new leprosy cases treated at a reference center in Fortaleza, Ceará from 2010 to 2013. The 16S rRNA gene region of M. leprae was amplified by qPCR and a standard curve was created with the pIDTBlue 16SrRNAMlep plasmid. The Juazeiro do Norte water samples and the biopsies were genotyped (single nucleotide polymorphism [SNP] 1 to 4) and the SNP 4 genotypes were subtyped. RESULTS: Of the 149 water samples analyzed, 54.4% were positive for the M. leprae DNA. The M. leprae bacilli copy number ranged from 1.42 × 10 -1 to 1.44 × 10 + 2 . Most biopsies showed SNP type 4 (64%), while all samples from Juazeiro do Norte were SNP type 4, with subtype 4-N appearing at the highest frequency. CONCLUSIONS: We suggest that environmental waters containing M. leprae bacilli play an important role in disease transmission, justifying PGL-1 seropositivity in individuals living in areas where there is no reported case, and in leprosy cases individuals who report no previous contact with other case. Therefore, further investigation is needed to clarify disease transmission in this region and to explore the role of the environment. We also suggest that in this area surveillance for leprosy cases should be intensified.

A case-control study was conducted to determine the presence ofMycobacterium leprae DNA in nasal secretions of leprosy cases and nonleprosy individuals in Fortaleza, Brazil. It included 185 cases identified by physicians at the Dona Libânia National Reference Centre for Sanitary Dermatology (CDERM). A control group (Co) (n = 136) was identified among individuals from CDERM not diagnosed as leprosy cases. To augment the spatial analysis of M. leprae specific repetitive element (RLEP) positive prevalence, an external group (EG) (n = 121), a convenience sample of healthy students, were included. Polymerase chain reaction for the RLEP sequence was conducted for all participants. Prevalence of RLEP positivity for cases and Co were 69.2% and 66.9%, respectively, significantly higher than for EG (28.1%), and reported elsewhere. Male sex, belonging to a lower socioeconomic status (D/E), history of a previous contact with a case and being older, were associated with being a leprosy case. Our geographical analysis demonstrated that the bacillus is widespread among the healthy population, with clusters of RLEP positive multibacillary cases concentrated in distinct areas of the city. Our results suggest that in endemic areas, as in Fortaleza, surveillance for both nonhousehold leprosy contacts and members of the general population living in cluster areas should be implemented.

Objetivo: Comparar desfechos intrahospitalares em pacientes submetidos a cirurgia da aorta torácica e toracoabdominal, antes e após a constituição do Centro Especializado de Tratamento da Aorta (CTA). Métodos: Coorte prospectiva com controle não contemporâneo. A criação do CTA envolveu treinamento cirúrgico especializado, sala híbrida, monitorização neurológica, capacitação de pessoal de apoio, aperfeiçoamento dos registros e uso de protocolos específicos. Foram incluídos 332 pacientes operados em 2 períodos: janeiro/2003 a dezembro/2007 (pré-CTA, n=157, 47,3%); e janeiro/2008 a dezembro/2010 (CTA, n=175, 52,7%). As características demográficas, clínicas, dados cirúrgicos, complicações e mortalidade hospitalar foram comparados nos 2 grupos. Resultados: A idade média foi 58±14 anos, com 65% sexo masculino. O grupo CTA teve idade, prevalência de diabete (DM) e glicemia maiores; menor prevalência de doença pulmonar obstrutiva crônica e insuficiência cardíaca; maior proporção de aneurismas e cirurgias eletivas; e mais procedimentos endovasculares que o pré-CTA. Na análise univariada, o grupo CTA mostrou redução de mortalidade (9,7% x 23,0%, P=0,008), que foi consistente nos diferentes subgrupos estratificados por patologia e por procedimento. O grupo CTA teve também redução de reoperações (5,7% x 11%, P=0,046), complicações maiores (20,6% x 33,1%, P=0,007), acidente vascular cerebral (4,6% x 10,9%, P=0,045) e sepse (1,7% x 9,6%, P=0,001), comparado ao pré-CTA. Na análise multivariada, o CTA se associou de forma independente a redução de mortalidade hospitalar (OR=0,23, IC 95% 0,08 - 0,67, P=0,007). A redução de mortalidade do CTA também ocorreu na análise estratificada por patologia (cirurgias de aneurisma, OR=0,18, IC 95% 0,03 - 0,98, P=0,048; cirurgias de dissecção, OR=0,31, IC 95% 0,09 - 0,99, P=0,049) e por procedimento (híbridos, OR=0,07, IC 95% 0,007 - 0,72, P=0,026; Bentall, OR=0,18, IC 95% 0,038 – 0,904, P=0,037). Também foram preditores independentes de mortalidade a creatinina pré-operatória (OR=1,7, IC 95% 1,1-2,6, P=0,008), a cirurgia de urgência (OR=5,0, IC 95% 1,5-16,7, P=0,008) e o aneurisma toracoabdominal (OR=24,6, IC 95% 3,1-194,1, P=0,002). Conclusão: O tratamento cirúrgico de patologias da aorta torácica e toracoabdominal em centro especializado, em comparação ao tratamento usual, se associou a menor incidência de complicações e mortalidade global.

Objective: To compare in-hospital outcomes in aortic surgery in our cardiac surgery unit, before and after foundation of our Center for Aortic Surgery (CTA). Methods: Prospective cohort with non-concurrent control. Foundation of CTA required specialized training of surgical, anesthetic and intensive care unit teams, routine neurological monitoring, endovascular and hybrid facilities, training of the support personnel, improvement of the registry and adoption of specific protocols. We included 332 patients operated on between: January/2003 to December/2007 (before-CTA, n=157, 47.3%); and January/2008 to December/2010 (CTA, n=175, 52.7%). Baseline clinical and demographic data, operative variables, complications and in-hospital mortality were compared between both groups. Results: Mean age was 58±14 years, with 65% male. Group CTA was older, had higher rate of diabetes, lower rates of COPD and HF, more non-urgent surgeries, endovascular procedures, and aneurysms. In the univariate analysis, CTA had lower mortality (9.7 vs. 23.0%, P=0.008), which occurred consistently across different diseases and procedures. Other outcomes which were reduced in CTA included lower rates of reinterventions (5.7 vs 11%, P=0.046), major complications (20.6 vs. 33.1%, P=0.007), stroke (4.6 vs. 10.9%, P=0.045) and sepsis (1.7 vs. 9.6%, P=0.001), as compared to before-CTA. Multivariable analysis adjusted for potential counfounders revealed that CTA was independently associated with mortality reduction (OR=0.23, IC 95% 0.08 – 0.67, P=0.007). CTA independent mortality reduction was consistent in the multivariable analysis stratified by disease (aneurysm, OR=0.18, CI 95% 0.03 – 0.98, P=0.048; dissection, OR=0.31, CI 95% 0.09 – 0.99, P=0.049) and by procedure (hybrid, OR=0.07, CI 95% 0.007 – 0.72, P=0.026; Bentall, OR=0.18, CI 95% 0.038 – 0.904, P=0.037). Additional multivariable predictors of in-hospital mortality included creatinine (OR=1.7 [1.1-2.6], P=0.008), urgent surgery (OR=5.0 [1.5-16.7], P=0.008) and thoracoabdominal aneurysm (OR=24.6 [3.1-194.1], P=0.002). Conclusion: Thoracic aorta surgery in specialized center was associated with lower incidence of complications and all-cause mortality as compared to usual care.

INTRODUÇÃO: Estima-se em mais de dois bilhões o número de infectados pelo Mycobacterium tuberculosis no mundo. A interleucina-6 (IL-6) é uma importante citocina, cujos níveis séricos estão comumente elevados na tuberculose pulmonar ativa. A dosagem dessa citocina em contatos de pacientes com tuberculose pode ser útil para se acompanhar a evolução do processo infeccioso, bem como para inferir o risco de progressão da doença ativa. OBJETIVO: Avaliar os níveis séricos de IL-6 em contatos de pacientes com tuberculose pulmonar ativa e compará-los com os de dois outros grupos: a) pacientes acometidos por tuberculose pulmonar ativa; b) não contatos de tuberculose. MÉTODOS: Estudo transversal com 15 contatos de pacientes com tuberculose pulmonar ativa, selecionados de acordo com protocolo preconizado pelo Ministério da Saúde. Os níveis séricos de IL-6 foram mensurados por meio de ensaio imunoenzimático (ELISA). O mesmo ensaio também foi empregado nos dois grupos de comparação: 38 pacientes com tuberculose pulmonar ativa (confirmada por exame clínico, raios X de tórax e baciloscopia) e 63 não contatos, doadores saudáveis de sangue. RESULTADOS: Para o grupo de contatos, a mediana de concentração de IL-6 foi de 1,7 pg/ml (0,96-4,8 pg/ml); para os acometidos por tuberculose pulmonar ativa e indivíduos não contatos, esses valores foram 4,3 pg/ml (0-12 pg/ml) e 0,5 pg/ml (0-2,8 pg/ml), respectivamente (p < 0,0001). CONCLUSÃO: Contatos de pacientes com tuberculose pulmonar ativa apresentaram níveis séricos de IL-6 significativamente aumentados (3,4 vezes mais), em relação aos indivíduos não contatos, mas em um patamar inferior (2,5 vezes menos), quando comparados com os acometidos pela doença ativa.

INTRODUCTION: It is estimated that over two billion individuals are infected by Mycobacterium tuberculosis worldwide. Interleukin-6 (IL-6) is an important cytokine whose serum levels are commonly high in active pulmonary tuberculosis (TB). IL-6 screening in contacts of patients with TB may be useful to monitor the progress of the infectious process and to infer the risk of progression to active disease. OBJECTIVE: To evaluate the serum levels of interleukin-6 in contacts of patients with active pulmonary tuberculosis and to compare them with two other groups: a) patients affected by active pulmonary tuberculosis; b) non-contacts of tuberculosis. METHODS: Cross-sectional study with 15 contacts of patients with active pulmonary tuberculosis, selected according to the protocol recommended by the Ministry of Health. The serum levels of interleukin-6 were measured by Enzyme-linked immunosorbent assay (ELISA). The same test was also applied in the two comparison groups: 38 patients with active pulmonary tuberculosis (confirmed by clinical examination, X-rays of the chest and baciloscopy) and 63 non-contacts (healthy blood donors). RESULTS: In the contact group, the median IL-6 concentration was 1.7 pg/ml (0.96-4.8 pg/ml). For those affected by active pulmonary tuberculosis and non-contact individuals, these values corresponded to 4.3 pg/ml (0.5-24 pg/ml) and 0.5 pg/ml (0-2.8 pg/ml), respectively (p < 0.0001). CONCLUSION: Contacts of patients with active pulmonary tuberculosis had significantly higher IL-6 serum levels (3.4 times higher) in relation to non-contact individuals, but on a lower level (2.5 times lower) when compared to those affected by active disease.

OBJECTIVES: This study has used a combination of clinical information, spoligotyping, and georeferencing system to elucidate the genetic diversity of the Mycobacterium tuberculosis isolates circulating in a TB-prevalent municipality of Northeast Brazil. METHODS: A total of 115 M. tuberculosis strains were isolated from pulmonary tuberculosis patients from January 2007 to March 2008 in Fortaleza. Drug susceptibility and spoligotyping assays were performed and place of residence of the patients were georeferenced. RESULTS: Of the M. tuberculosis strains studied, 51 (44.3%) isolates were resistant to at least one drug (R-TB) and 64 (55.7%) were sensitive to all the drugs tested (S-TB). A high frequency of resistance was found in previously treated cases (84%) and among new cases (16%; p < 0.001). a total of 74 (64%) isolates were grouped into 22 spoligotyped lineages, while 41 (36%) isolates were identified as new. among the predominant genotypes, 33% were latim american mediterranean (lam), 12% haarlem (h), and 5% u. there was no association of geographic distribution of rt-tb patients as compared to the controls and also the geographic location to the spoligotype patterns. the geospatial analysis revealed that 24 (23%) patients (hot spot zones) either shared the same residence or lived in a close neighborhood of a case. among these concentration zones, the patients lived in the same residence and shared a common genotype pattern and resistance pattern. DISCUSSION: it was observed that the spoligopatterns family distribution was similar to that reported for south america, prevailing the lam and h lineages. a high rate-case among the resistant TB group occurs as a result of transmitted and acquired resistance. A more effective surveillance program is needed in order to succeed in reducing tuberculosis in Northeast Brazil.

Human beings are the main reservoir of the causative agent of leprosy, Mycobacterium leprae. In the Americas, nine-banded armadillos (Dasypus novemcinctus) also act as a reservoir for the bacillus. In the state of Ceará (CE), which is located in Northeast Brazil and is an endemic area of leprosy, there are several species of armadillos, including D. novemcinctus and Euphractus sexcinctus (six-banded armadillo). Contact between humans and armadillos occur mainly through hunting, cleaning, preparing, cooking and eating. This study identified M. leprae DNA in the two main species of armadillos found in Northeast Brazil. A total of 29 wild armadillos (27 D. novemcinctus and 2 E. sexcinctus) were captured in different environments of CE countryside. Samples from the ear, nose, liver and spleen from each of these animals were tested by a nested M. leprae-specific repetitive element polymerase chain reaction assay. The samples that tested positive were confirmed by DNA sequencing. M. leprae was detected in 21% (6/29) of the animals, including five D. novemcinctus and one E. sexcinctus. This is the first Brazilian study to identify the presence of a biomarker of M. leprae in wild armadillos (D. novemcinctus and E. sexcinctus) in a leprosy hyperendemic area where there is continuous contact between humans and armadillos.

Infection with both Human Immunodeficiency Virus (HIV) and Mycobacterium tuberculosis is currently the world's leading cause of death due to infectious agents. We evaluated factors related to the development of tuberculosis (TB) in HIV-infected patients who were being treated at an infectious diseases hospital in Fortaleza, Ceará, Brazil. From January 2004 to December 2005, we made an epidemiological study through the analysis of the medical records of 171 patients, who were diagnosed as having both HIV and tuberculosis. Among these co-infected patients, most (81%, p=0.0006) were male. Co-infection was more frequent (87.8%) among patients over 40 years of age and those with lower educational levels (less than eight years of schooling). Forty-one percent of the patients in the study had not had a smear culture test for acid-fast bacilli (AFB). CD4 cell counts were lower than 200 cells/µL in 71.9% of the patients, the mean being 169 cells/µL. This type of data is important for establishing strategies to improve the control of tuberculosis in HIV-infected patients.

Entre 1834 bacilos Gram-Negativos isolados no complexo hospitalar da Universidade Federal do Ceará - Brasil no período de janeiro de 1995 à fevereiro de 1996, 456 (24,8%) foram Bacilos Gram-Negativos Não Fermentadores (BGNNF). Este estudo relata sua identificação a nível de espécie e sua freqüência. Treze gêneros e trinta espécies foram identificadas, sendo que Pseudomonas aeruginosa foi a espécie mais freqüente (69,95%) seguida por Acinetobacter baumannii (5,48%) e Acinetobacter lwoffii (3,95%). Entre as cepas identificadas como P. aeruginosa, 94,1 % foram produtoras de pigmentos, mas 7,9% delas produziram pigmento somente após diversos subcultivos. A freqüência da maioria das espécies identificadas foi similar à relatada na literatura.

Among one thousand eight hundred and thirty-four Gram-negative bacilli, isolated at Universidade Federal do Ceará hospital complex - Brazil, from January 1995 to February 1996, 456 (24.8%) were Nonfermentative Gram-Negative Bacilli (NFGNB). This study reports their identification to the species level and their frequency as well. Thirteen genera and thirty species were identified and Pseudomonas aeruginosa was the most frequent species (69.95%), followed by Acinetobacter baumannii (5.48%) and by Acinetobacter lwoffii (3.95%). Among the identified P.aeruginosa strains, 94.1% produced pigment but 7.9% of them produced pigment only after being cultivated several times. The frequency of the most species was similar to that reported in the literature.