Ferrets as a model for tuberculosis transmission.

Even with the COVID-19 pandemic, tuberculosis remains a leading cause of human death due to a single infectious agent. Until successfully treated, infected individuals may continue to transmit Mycobacterium tuberculosis bacilli to contacts. As with other respiratory pathogens, such as SARS-CoV-2, modeling the process of person-to-person transmission will inform efforts to develop vaccines and therapies that specifically impede disease transmission. The ferret (Mustela furo), a relatively inexpensive, small animal has been successfully employed to model transmissibility, pathogenicity, and tropism of influenza and other respiratory disease agents. Ferrets can become naturally infected with Mycobacterium bovis and are closely related to badgers, well known in Great Britain and elsewhere as a natural transmission vehicle for bovine tuberculosis. Herein, we report results of a study demonstrating that within 7 weeks of intratracheal infection with a high dose (>5 x 103 CFU) of M. tuberculosis bacilli, ferrets develop clinical signs and pathological features similar to acute disease reported in larger animals, and ferrets infected with very-high doses (>5 x 104 CFU) develop severe signs within two to four weeks, with loss of body weight as high as 30%. Natural transmission of this pathogen was also examined. Acutely-infected ferrets transmitted M. tuberculosis bacilli to co-housed naïve sentinels; most of the sentinels tested positive for M. tuberculosis in nasal washes, while several developed variable disease symptomologies similar to those reported for humans exposed to an active tuberculosis patient in a closed setting. Transmission was more efficient when the transmitting animal had a well-established acute infection. The findings support further assessment of this model system for tuberculosis transmission including the testing of prevention measures and vaccine efficacy.

Evaluation of a temperature-restricted, mucosal tuberculosis vaccine in guinea pigs.

Tuberculosis (TB) is currently the leading cause of death in humans by a single infectious agent, Mycobacterium tuberculosis. The Bacillus Calmette-Guérin (BCG) vaccine prevents pulmonary TB with variable efficacy, but can cause life-threatening systemic infection in HIV-infected infants. In this study, TBvac85, a derivative of Mycobacterium shottsii expressing M. tuberculosis Antigen 85B, was examined as a safer alternative to BCG. Intranasal vaccination of guinea pigs with TBvac85, a naturally temperature-restricted species, resulted in serum Ag85B-specific IgG antibodies. Delivery of the vaccine by this route also induced protection equivalent to intradermal BCG based on organ bacterial burdens and lung pathology six weeks after aerosol challenge with M. tuberculosis strain Erdman. These results support the potential of TBvac85 as the basis of an effective TB vaccine. Next-generation derivatives expressing multiple M. tuberculosis immunogens are in development.

Severe Dermatitis Associated with Spontaneous Staphylococcus xylosus Infection in Rag-/-Tpl2-/- Mice.

Staphylococcus xylosus is a commensal bacterium found on the skin and mucosal surfaces of SPF mice. S. xylosus is rarely pathogenic, most often causing skin lesions and dermatitis in immunocompromised mice, particularly those with impaired NADPH oxidase function. Here we report spontaneous infection with S. xylosus in Rag1-/-Tpl2-/- mice. Infection was characterized by the presence of alopecia, crusts, and scaly skin. S. xylosus was detected in the feces, skin, lymph nodes, and lungs of Rag1-/-Tpl2-/- mice and led to mortality or euthanasia due to humane endpoints. C57BL/6 mice were culture-positive for S. xylosus on the skin, and Rag1-/- and Tpl2-/- mice were culture-positive on the skin and occasionally in the feces. However, S. xylosus did not cause clinical symptoms in C57BL/6, Rag1-/-, or Tpl2-/- mice. Compared with those in Rag1-/- mice, relative concentrations of circulating monocytes, but not neutrophils or lymphocytes, were increased in Rag1-/-Tpl2-/- mice, consistent with their increased incidence of clinical symptoms. Overall, this case study suggests a novel role for Tpl2 in T-cell-independent host resistance to the otherwise commensal organism S. xylosus.

[Radiotherapy for pancreatic cancer]. / Radioterapia em adenocarcinoma de pâncreas.

BACKGROUND: The pancreatic adenocarcinoma is an aggressive disease for which cure is only possible in less than 20% of the best cases. Adjuvant radiotherapy and chemotherapy so far have improved symptoms with little, but significant, increase in survival rates. METHODS: Retrospective assessment of 40 patients admitted at Department of Radiation Oncology of the Hospital Israelita Albert Einstein between April 1993 and August 1999 was done. Radical surgery with tumor resection was previously performed in 25 and palliative procedures or nothing in 15. RESULTS: Overall actuarial median survival was 14.8 months; and actuarial survival rates at 12 and 24 months were 70% and 22.2% respectively. Actuarial median survival for the group of patients with resected tumor was 21.4 and for the group of patients with non-resected tumor was 16.1 months. Expected survival rates at 12 and 24 months were 76% and 32% for the former group and 60% and 0% for the latter. CONCLUSIONS: Results were similar to other published series. Better drugs and more frequent intraoperative radiotherapy are necessary.

Radioterapia em adenocarcinoma de pâncreas / Radiotherapy for pancreatic cancer

OBJETIVO: Avaliar retrospectivamente a sobrevida dos pacientes portadores de adenocarcinoma de pâncreas tratados no Serviço de Radioterapia do Hospital Israelita Albert Einstein, comparando os resultados com a literatura, e apresentando proposta de conduta. MÉTODOS: Entre abril de 1993 e agosto de 1999, 40 pacientes com adenocarcinoma de pâncreas foram admitidos para radioterapia neste Serviço. Destes, 25 haviam sido submetidos a procedimento cirúrgico radical com ressecçäo do tumor e em 15 o tumor näo havia sido ressecado (näo operados, biopsiados apenas ou submetidos a intervençöes cirúrgicas paliativas). RESULTADOS: A sobrevida actuarial mediana para toda amostra foi de 14,8 meses, sendo as probabilidades de sobrevida em 12 e 24 meses, 70 por cento e 22,2 por cento, respectivamente. A sobrevida actuarial mediana para o grupo de pacientes que tiveram o tumor ressecado foi de 21,4 meses e para o grupo de pacientes com tumor näo ressecado, 16,1 meses, sendo a probabilidade de sobreviver 12 e 24 meses de 76 por cento e 32 por cento no primeiro grupo e 60 por cento e 0 por cento no segundo (p=0,0156). CONCLUSÖES: Os nossos resultados säo semelhantes aos descritos na literatura médica atual. Há necessidade de introduzir novas drogas ativas para o tratamento destes tumores e a radioterapia intra-operatória tem que ser melhor explorada

Intracoronary brachytherapy in the treatment of in-stent restenosis. Initial experience in Brazil

Intracoronary brachytherapy using beta or gamma radiation is currently the most efficient type of therapy for preventing the recurrence of coronary in-stent restenosis. Its implementation depends on the interaction among interventionists, radiotherapists, and physicists to assure the safety and quality of the method. The authors report the pioneering experience in Brazil of the treatment of 2 patients with coronary in-stent restenosis, in whom beta radiation was used as part of the international multicenter randomized PREVENT study (Proliferation REduction with Vascular ENergy Trial). The procedures were performed rapidly and did not require significant modifications in the traditional techniques used for conventional angioplasty. Alteration in the radiological protection devices of the hemodynamic laboratory were also not required, showing that intracoronary brachytherapy using beta radiation can be incorporated into the interventional tools of cardiology in our environment

Procedimentos para pacientes portadores de marcapasso e submetidos à radioterapia / Procedures for radiation therapy in patients using cardiac pacemarkers

Os modernos marcapassos cardíacos podem falhar quando submetidos a radiaçäo ionizante da ordem de 10 Gy e exibir alteraçös funcionais com doses täo baixas quanto 2 Gy. A interferência eletromagnética também pode afetar seu desempenho, mas este efeito näo é problema sério quando consideramos os equipamentos de radioterapia atuais. Devido ao aumento significativo de aceleradores lineares no Brasil e, com isto, um aumento da probabilidade de tratamento de pacientes portadores de marcapassos cardíacos permanentes com esses equipamentos, apresentamos uma revisäo e discussäo dos problemas em potencial associados e sugerimos alguns cuidados que adotamos e praticamos no Serviço de Radioterapia do Hospital Israelita Albert Einstein