A common approach for fighting tuberculosis and leprosy: controlling endoplasmic reticulum stress in myeloid-derived suppressor cells.

Leprosy and tuberculosis are infectious diseases that are caused by bacteria, and both share primary risk factors. Mediators of these diseases are regulated by a heterogeneous immature population of myeloid cells called myeloid-derived suppressor cells (MDSCs) that exhibit immunosuppressive activity against innate and adaptive immunity. During pathological conditions, endoplasmic reticulum (ER) stress occurs in MDSCs, and high levels of ER stress affect MDSC-linked immunosuppressive activity. Investigating the role of ER stress in regulating immunosuppressive functions of MDSCs in leprosy and tuberculosis may lead to new approaches to treating these diseases. Here the authors discuss the immunoregulatory effects of ER stress in MDSCs as well as the possibility of targeting unfolded protein response elements of ER stress to diminish the immunosuppressive activity of MDSCs and reinvigorate diminished adaptive immune system responses that occur in leprosy and tuberculosis.

Economic evaluation of patient costs associated with tuberculosis diagnosis and care in Solomon Islands.

BACKGROUND: Tuberculosis (TB) care can be costly for patients and their families. The End TB Strategy includes a target that zero TB affected households should experience catastrophic costs associated with TB care. Costs are catastrophic when a patient spends 20% or more of their annual household income on their TB diagnosis and care. In Solomon Islands the costs of TB care are unknown. The aim of this study was to determine the costs of TB diagnosis and care, the types of costs and the proportion of patients with catastrophic costs. METHODS: This was a nationally representative cross-sectional survey of TB patients carried out between 2017 and 2019. Patients were recruited from health care facilities, from all ten provinces in Solomon Islands. During an interview they were asked about the costs of TB diagnosis and care. These data were analysed using descriptive statistics to describe the costs overall and the proportions of different types of costs. The proportion of patients with catastrophic costs was calculated and a multivariate logistic regression was undertaken to determine factors associated with catastrophic costs. RESULTS: One hundred and eighty-three TB patients participated in the survey. They spent a mean of 716 USD (inter quartile range: 348-1217 USD) on their TB diagnosis and care. Overall, 62.1% of costs were attributable to non-medical costs, while income loss and medical costs comprised 28.5 and 9.4%, respectively. Overall, 19.7% (n = 36) of patients used savings, borrowed money, or sold assets as a financial coping mechanism. Three patients (1.6%) had health insurance. A total of 92.3% (95% CI: 88.5-96.2) experienced catastrophic costs, using the output approach. Being in the first, second or third poorest wealth quintile was significantly associated with catastrophic costs (adjusted odds ratio: 67.3, 95% CI: 15.86-489.74%, p <  0.001). CONCLUSION: The costs of TB care are catastrophic for almost all patients in Solomon Islands. The provision of TB specific social and financial protection measures from the National TB and Leprosy Programme may be needed in the short term to ameliorate these costs. In the longer term, advancement of universal health coverage and other social and financial protection measures should be pursued.

A case of febrile ulceronecrotic Mucha-Habermann disease with comorbidities.

Febrile ulceronecrotic Mucha-Habermann disease is a very rare and severe variant of pityriasis lichenoides et varioliformis acuta. Adult cases are difficult to diagnose as in the early course they can mimic erythema multiforme or lymphomatoid papulosis. We report a case of a 38-year-old woman who presented with 90% body surface area involvement, fever, diarrhea, malaise and associated comorbidities. She was treated with systemic steroids and methotrexate but suffered a fatal outcome. So far, a total of 65 cases are reported in the literature.

A clausura enferma: petições para a saída do Convento da Ajuda no Rio de Janeiro para tratamento de doenças contagiosas, c. 1750-1780 / Disease in the cloisters: requests to leave Convento da Ajuda, Rio de Janeiro, for the treatment of contagious diseases, c. 1750-1780

Resumo O artigo discute os pedidos de freiras do Convento da Ajuda para deixar a clausura a fim de curar doenças contagiosas. O padecimento dessas doenças era considerado uma das poucas exceções para permitir a saída das freiras. As ordens femininas guardavam estritamente a clausura, condição necessária para manter o recato de virgens consagradas a Cristo. A documentação contém detalhes sobre as causas e as formas de transmissão das doenças, bem como sobre os tipos de tratamento para combatê-las. Por fim, os processos esclarecem os procedimentos adotados fora da clausura para as freiras não colocarem em risco o recolhimento e a honra, quando iam buscar em locais distantes o tratamento adequado para aquelas doenças.

Abstract This article discusses the requests submitted by nuns from Convento da Ajuda (Ajuda Convent) to leave their life of enclosure to receive treatment for contagious diseases. Disease was one of the few cases in which nuns were granted permission to leave. The female orders were strictly cloistered in order to preserve their purity as virgins consecrated to Christ. Extant documents detail the causes of the diseases, the ways they were transmitted, and the treatments used to fight them. These processes shed light on the procedures adopted outside the cloisters so that the nuns did not jeopardize their reclusion and honor when they went to distant places in search of treatment.

[Disease in the cloisters: requests to leave Convento da Ajuda, Rio de Janeiro, for the treatment of contagious diseases, c.1750-1780]. / A clausura enferma: petições para a saída do Convento da Ajuda no Rio de Janeiro para tratamento de doenças contagiosas, c.1750-1780.

This article discusses the requests submitted by nuns from Convento da Ajuda (Ajuda Convent) to leave their life of enclosure to receive treatment for contagious diseases. Disease was one of the few cases in which nuns were granted permission to leave. The female orders were strictly cloistered in order to preserve their purity as virgins consecrated to Christ. Extant documents detail the causes of the diseases, the ways they were transmitted, and the treatments used to fight them. These processes shed light on the procedures adopted outside the cloisters so that the nuns did not jeopardize their reclusion and honor when they went to distant places in search of treatment.

[Understanding current practice of clinical medicine in the tropics (II). Bacterial and viral diseases. Malnutrition]. / Aspectos básicos en la práctica actual de la medicina clínica en el trópico (II). Enfermedades bacterianas y virales. Malnutrición.

In recent years, a significant number of physicians want to spend part of their medical training in health facilities in developing countries. In this setting, clinical skills are extremely important due to the limited available diagnostic resources. Bacterial diseases are common, but bacterial cultures are rarely accessible. In Africa, tuberculosis affects over 200 cases per 100,000 persons, and more than 22 million people live with HIV infection; both diseases are a serious public health problem. Malnutrition is endemic in many countries in Africa and is compounded by the continuous humanitarian and food crisis. In this paper, basic concepts of epidemiology, clinical features, diagnosis and treatment of major diseases that can be found in a rural health post in the tropics are discussed.

Planning for PPM-DOTS implementation in urban slums in Kenya: knowledge, attitude and practices of private health care providers in Kibera slum, Nairobi.

SETTING: Kibera, the largest slum in Nairobi, Kenya. OBJECTIVE: To determine the tuberculosis (TB) knowledge, attitude and practices (KAP) of private health care providers (PHCPs) to identify their training needs and willingness to participate in a National Leprosy and Tuberculosis Control Programme (NLTP) guided TB control effort in the slum. DESIGN AND METHODOLOGY: A cross-sectional survey. The KAP of PHCPs was assessed using an interviewer administered questionnaire. RESULTS: Of 75 PHCPs interviewed, the majority (96.0%) were paramedics; 51 (77.1%) did not consider sputum smear microscopy crucial in patients presenting with prolonged cough or when a chest X-ray was suggestive of TB; of 29 (38.7%) who indicated familiarity with the drugs used in TB treatment, 20 (58.5%) would have chosen the NLTP-recommended regimens for the treatment of the various types of TB; 16 (21.3%) PHCPs indicated that they treated TB, six (37.5%) of whom were not familiar with anti-tuberculosis drug regimens. All the PHCPs referred TB suspects to the public sector for diagnosis. CONCLUSION: This study reveals a significant gap in TB knowledge among the PHCPs in Kibera slum. However, given appropriate training and supervision, there is potential for public-private mix for DOTS implementation in this setting.

Immunotherapy with plasmid DNA encoding mycobacterial hsp65 in association with chemotherapy is a more rapid and efficient form of treatment for tuberculosis in mice.

Tuberculosis (TB) remains a threat for public health, killing around 3 million people a year. Despite the fact that most cases can be cured with antibiotics, the treatment is long and patients relapse if chemotherapy is not continued for at least 6 months. Thus, a better characterization of the working principles of the immune system in TB and identification of new immunotherapeutic products for the development of shorter regimens of treatment are essential to achieve an effective management of this disease. In the present work, we demonstrate that immunotherapy with a plasmid DNA encoding the Mycobacterium leprae 65 kDa heat-shock protein (hsp65) in order to boost the efficiency of the immune system, is a valuable adjunct to antibacterial chemotherapy to shorten the duration of treatment, improve the treatment of latent TB infection and be effective against multidrug-resistant bacilli (MDR-TB). We also showed that the use of DNA-hsp65 alone or in combination with other drugs influence the pathway of the immune response or other types of inflammatory responses and should augment our ability to alter the course of immune response/inflammation as needed, evidencing an important target for immunization or drug intervention.

Software de programação dos medicamentos tuberculostáticos e Hansenostáticos

A Tuberculose e a Hanseníase são doenças que ocorrem em grande parte da população brasileira, independente da idade e do sexo, mas com maior prevalência nas classes sociais menos favorecidas, o que torna essas doenças de interesse prioritário para o Ministério da Saúde, que considerou os programas nacionais como estratégicos, desenvolvendo várias ações para o seu controle e erradicação. Como a garantia do acesso ao medicamento é a principal ação para o controle desses agravos, torna-se necessária a elaboração da programação e distribuição dos medicamentos, evitando o desabastecimento e perdas, como ocorrido na sistemática adotada nas programações até o ano 2000. Neste sentido, tornou-se essencial elaborar um software de programação de medicamentos tuberculostáticos e hansenostáticos. No final de 2000, a Secretaria de Políticas de Saúde, por meio da Gerência Técnica de Assistência Farmacêutica – GTAF, constituiu um grupo de trabalho, composto por técnicos da GTAF e da Área Técnica de Pneumologia e Dermatologia Sanitária do MS e consultores de alguns estados, com a finalidade de elaborar o instrumento. O software foi elaborado baseado em critérios epidemiológicos e técnicos e implantado nas 27 Unidades Federadas, as quais utilizaram o instrumento nas programações de 2002 e 2003 e desenvolveram um plano de trabalho para a implantação em todos os seus municípios. A utilização do software na programação promoveu: diminuição da aquisição da maioria dos medicamentos por parte do MS, sem gerar desabastecimento; redução significativa das perdas; aproveitamento dos quantitativos excedentes da programação em curso; adequação da distribuição estadual de medicamentos de acordo com os esquemas terapêuticos recomendados pelo MS; uniformização do esquema terapêutico utilizado pelas Coordenações Estaduais, entre outros. Na programação dos medicamentos hansenostáticos de 2002, em relação a 2001, a utilização do software propiciou uma diminuição da aquisição em média de (vinte e um porcento) da maioria dos medicamentos, em 2003, em relação a 2002, reduziu em média (trinta e oito porcento). Na programação dos medicamentos tuberculostáticos de 2002, em relação a 2001, reduziu a aquisição em média (quarenta e oito porcento) , sendo que para a Isoniazida 100mg com., chegou a (noventa e quatro porcento)

Comparative mycobacterial genomics as a tool for drug target and antigen discovery.

Genomics and the associated downstream technologies are generating vast data sets that provide new opportunities for understanding and combating both infectious and genetic diseases in humans. The genomic approach has been applied to tuberculosis, a major cause of transmissible morbidity and mortality, with notable success. Complete genome sequences are now available for three members of the Mycobacterium tuberculosis complex and the related intracellular pathogen M. leprae. Many of the predictions generated in silico by genomics have been validated through functional analysis, including studies of the transcriptome and proteome, and led to the identification of essential genes. Knowledge of the latter defines potential targets for new and existing drugs and their specificity can be assessed by comparative genomics with the host or other pathogens. Genomics is also furthering tuberculosis vaccine development by pinpointing potentially antigenic proteins as well as providing better diagnostic tools to detect infection.

Therapy of tuberculosis in mice by DNA vaccination.

Mycobacterium tuberculosis continues to kill about 3 million people every year, more than any other single infectious agent. This is attributed primarily to an inadequate immune response towards infecting bacteria, which suffer growth inhibition rather than death and subsequently multiply catastrophically. Although the bacillus Calmette-Guerin (BCG) vaccine is widely used, it has major limitations as a preventative measure. In addition, effective treatment requires that patients take large doses of antibacterial drug combinations for at least 6 months after diagnosis, which is difficult to achieve in many parts of the world and is further restricted by the emergence of multidrug-resistant strains of M. tuberculosis. In these circumstances, immunotherapy to boost the efficiency of the immune system in infected patients could be a valuable adjunct to antibacterial chemotherapy. Here we show in mice that DNA vaccines, initially designed to prevent infection, can also have a pronounced therapeutic action. In heavily infected mice, DNA vaccinations can switch the immune response from one that is relatively inefficient and gives bacterial stasis to one that kills bacteria. Application of such immunotherapy in conjunction with conventional chemotherapeutic antibacterial drugs might result in faster or more certain cure of the disease in humans.