Disseminated Forms Of Tuberculosis Research Articles

Clinical and Epidemiological Features of Tuberculosis in Ukraine (Review)

The analysis of professional publications regarding the clinical and epidemiological features of tuberculosis in contemporary conditions was conducted. Literature review indicates that tuberculosis remains a pressing issue in Ukraine, particularly amidst the conditions of military conflict and active hostilities. The characteristics of multidrug-resistant tuberculosis (MDR-TB) in children and adolescents from areas of drug-resistant tuberculosis infection have been studied. The onset of MDR-TB in children is often acute, while in adolescents, it tends to be insidious. Children and adolescents are particularly susceptible to the development of MDR-TB. Annually, 1.1 million patients under the age of 15 are diagnosed with tuberculosis, with approximately 700 children dying from tuberculosis daily.The features of detection and course of clinical forms of extrapulmonary tuberculosis and the profile of drug resistance of the pathogen in different age groups were analysed based on literature data. In 2022, more cases of extrapulmonary and disseminated forms of tuberculosis were registered compared to 2019 — 15.6 % and 8.1 %, respectively. Pulmonary tuberculosis was detected in 34.7 % in 2019 and 38.9 % in 2022.In contemporary conditions, the spread and development of tuberculosis are influenced by HIV infection and coronavirus disease 2019 (COVID-19). HIV infection contributes to a tuberculosis epidemic, affecting the course and outcomes of its treatment. Stigmatisation regarding COVID-19 and fear of quarantine hindered and delayed patients seeking medical care, limiting their mobility and leading to a decrease in most medical services for the diagnosis, treatment and prevention of tuberculosis.The situation in Ukraine (prevalence of HIV infection and COVID-19, military actions in the country, population migration, presence of refugees and internally displaced persons) has also contributed to the development and spread of tuberculosis, increasing the incidence and mortality rates from this disease, and progressing its burden. Among refugees, internally displaced persons and the population of territories where these individuals are located, tuberculosis, COVID-19 and HIV infection may concurrently spread.

Pulmonary and extrapulmonary and extrapulmonary in tubercular miliaria : disseminated forms of tuberculosis About 131 cases

Pulmonary and extrapulmonary and extrapulmonary in tubercular miliaria : disseminated forms of tuberculosis About 131 cases

Failure of BCG Necessitates to the Development of New Novel Vaccine

The only vaccine available for the deadly disease tuberculosis is Bacillus- Calmette-Guerin (BCG), which is an attenuated vaccine of Mycobacterium bovis. Although this vaccine boosts immune response but it is effective only for 10-20 years, after this there is need to develop immunity against Mycobacterium tuberculosis H37Rv (M. tuberculosis). As the vaccine is botched to provide sustained effects and to protect against disseminated forms of Tuberculosis (TB), it needs a component to heighten antigen specific immune reactions when used in combination with particular vaccine antigens that can also modulate the immune responses to an antigen to advance them. Adjuvants are the one such factor that can be used in vaccines to crack such problems. Many vaccines are under clinical trials in which subunit vaccine has taken attention because they are safer and can be standardized. There are many adjuvants which have been tested in combinations with BCG to increase the activity of vaccine. Mycobacterial antigen 85 A, B, C, present at outer part of cell wall and have great potential as therapeutic approach towards tuberculosis. MPT64 increases T-cell response in tuberculosis patients but there are less evidence about the role of this secreted mycobacterial protein in patients. ESAT 6 is effective T cell antigen and also pore forming toxin which is crucial for the virulence of bacterium. ESAT 6 separately or in compound form with its chaperone CFP- 10 form, regulates host immune response. They efficiently modify innate and adaptive immune response. This review provides an insight in the direction of the vaccine development on the basis of pre-existing credentials.

Bone Marrow Granuloma with Miliary Mottling presenting as Pancytopenia- A rare finding in Tuberculosis - A Case report

Bone marrow granuloma and miliary mottling presenting as pancytopenia together is a rare finding in disseminated form of tuberculosis. Here we report a case of a 52-year, old male patient presented with generalized weakness, loss of appetite, decreased physical activity for one month. Initial lab hematological investigations revealed pancytopenia and high Erythrocyte sedimentation rate. Bone marrow biopsy was performed to determine the cause of pancytopenia which showed caseating granulomas with positive acid fast bacilli on Ziehl-Neelsen staining (Z-N). In chest X-ray miliary mottling and bone marrow biopsy findings together confirmed the case of disseminated tuberculosis. This unusual presentation highlights the considerable diagnostic challenge and importance of bone marrow biopsy for early diagnosis and initiation of treatment.
 Mediscope Vol. 8, No. 1: January 2021, Page 63-66

Will bacille Calmette-Guerin immunization arrest the COVID-19 pandemic?

Will bacille Calmette-Guerin immunization arrest the COVID-19 pandemic?

Lingual tuberculosis: A rare presentation of disseminated form of tuberculosis

Lingual tuberculosis: A rare presentation of disseminated form of tuberculosis

Construction and Characterization of the Mycobacterium tuberculosis sigE fadD26 Unmarked Double Mutant as a Vaccine Candidate.

Despite the great increase in the understanding of the biology and pathogenesis of Mycobacterium tuberculosis achieved by the scientific community in recent decades, tuberculosis (TB) still represents one of the major threats to global human health. The only available vaccine (Mycobacterium bovis BCG) protects children from disseminated forms of TB but does not effectively protect adults from the respiratory form of the disease, making the development of new and more-efficacious vaccines against the pulmonary forms of TB a major goal for the improvement of global health. Among the different strategies being developed to reach this goal is the construction of attenuated strains more efficacious and safer than BCG. We recently showed that a sigE mutant of M. tuberculosis was more attenuated and more efficacious than BCG in a mouse model of infection. In this paper, we describe the construction and characterization of an M. tuberculosissigE fadD26 unmarked double mutant fulfilling the criteria of the Geneva Consensus for entering human clinical trials. The data presented suggest that this mutant is even more attenuated and slightly more efficacious than the previous sigE mutant in different mouse models of infection and is equivalent to BCG in a guinea pig model of infection.

Minipigs as a neonatal animal model for tuberculosis vaccine efficacy testing

Many vaccines against childhood diseases are administered early after birth, but vaccine development studies frequently test efficacy in adult rather than in neonatal animal models. In countries with endemic tuberculosis (TB), Bacillus Calmette-Guerin (BCG) is administered as part of the neonatal vaccine regimen because it prevents against the disseminated form of TB in children, although it has variable efficacy against pulmonary TB. Several promising new vaccines against TB are currently being tested in adult animal models. Here we evaluated neonatal piglets as an animal model to test vaccine efficacy. For this purpose, minipigs were vaccinated or not with BCG 48 h after birth and their immune response followed longitudinally until adolescence. We characterized the memory and activation phenotype of T cells, cytokine profile, and monocyte activation in response to BCG stimulation from 4 weeks of age into adolescence- age of 24 weeks. Immunological responses in vaccinated and non-vaccinated animals were further monitored upon infection with a low dose exposure to Mycobacterium tuberculosis strain HN878 via the aerosol route. Comparing the immunological response elicited by BCG vaccination in minipigs vs similar studies in infants, suggest that minipigs have the potential to serve as an effective neonatal animal model for vaccine development.

Scrofuloderma with disseminated tuberculosis in an Ethiopian child: a case report

BackgroundCutaneous tuberculosis represents only 1–2% of extrapulmonary forms of tuberculosis. Scrofuloderma is an endogenous form of cutaneous tuberculosis and can present as isolated or coexist with pulmonary and disseminated forms of tuberculosis. Pathologically confirmed scrofuloderma coexisting with disseminated tuberculosis with a good treatment response is presented and discussed.Case presentationA 12-year-old African Ethiopian girl presented with bilateral neck swelling with purulent discharge and skin ulceration of 3 months’ duration. Dry cough, low-grade fever, decreased appetite, drenching night sweats, global throbbing headache, and a significant amount of weight loss were also reported. Biopsy of the skin identified scrofuloderma, and Mycobacterium tuberculosis was also identified by Xpert MTB/RIF assay. Cerebrospinal fluid analysis and brain computed tomographic scans showed tuberculous meningitis and tuberculoma. Antituberculosis therapy with rifampicin, isoniazid, pyrazinamide, and ethambutol; prednisolone; pyridoxine; and wound care were provided. The patient was discharged for outpatient directly observed antituberculosis therapy in a nearby health center after acute complications were treated and once the skin lesion had started to dry or heal.ConclusionsCutaneous tuberculosis should be considered in a child presenting with a skin lesion or discharge. Cutaneous tuberculosis cases should be investigated for coexisting pulmonary and extrapulmonary forms of tuberculosis. Histopathologic diagnosis should be considered to rule out other skin pathologies and also to prevent delay in treatment. Better tuberculosis prevention strategies, including vaccination scale-up, are warranted.

Features of immunoregulation in patients with pulmonary tuberculosis with blood eosinophilia

The aimof the investigation was to determine the characteristics of the immune response regulation for pulmonary tuberculosis (TB) and to analyze the role of regulatory T cells in the immunopathogenesis of TB with eosinophilia in the blood, depending on the clinical form of the disease and sensitivity of Micobacterium tuberculosis to anti-TB drugs.Materials and methods.157 patients who were initially diagnosed with infiltrative and disseminated TB were examined. The material of the study was venous blood and culture of mononuclear leukocytes isolated from venous blood. The content of interleukin (IL) 4, IL-10 and transforming factor beta (TGFβ) in culture suspensions of mononuclear leukocytes in vitro and IL-5 in the blood was determined by enzyme-linked immunosorbent assay (ELISA) test. The expression of surface molecules CD4, CD20, CD25 and intracellular transcription factor Foxp3 by lymphocytes of the blood was evaluated by flow cytometry. The obtained results were analyzed by statistical methods.Results.It is shown that excessive generation of regulatory T cells in patients with TB is associated with eosinophilia of the blood and imbalance of immune response regulation mechanisms. In TB with eosinophilia, an increase in the number of Foxp3-positive regulatory T cells in the blood is combined with in vitro hypersecretion of anti-inflammatory cytokines TGFβ, IL-10, IL-4 and an increase in the content of CD20+ B lymphocytes and IL-5 in the blood. These changes are most pronounced in the disseminated form of TB in combination with drug resistance.Conclusion.Characteristics of immunoregulation at TB with blood eosinophilia are associated with activation of immunosuppression mechanisms and polarization of immune response towards Th2-dependent pathway.

Breaking Transmission with Vaccines: The Case of Tuberculosis.

Members of the Mycobacterium tuberculosis complex (MTBC) have evolved causing tuberculosis (TB) in different mammalian hosts. MTBC ecotypes have adapted to diverse animal species, with M. bovis being the most common cause of TB in livestock. Cattle-to-human transmission of M. bovis through ingestion of raw milk was common before introduction of the pasteurization process. TB in humans is mainly caused by M. tuberculosis. This bacterium is considered a genetically clonal pathogen that has coevolved with humans due to its ability to manipulate and subvert the immune response. TB is a major public health problem due to airborne person-to-person transmission of M. tuberculosis. The essential yet unanswered question on the natural history of TB is when M. tuberculosis decides to establish latent infection in the host (resambling the lysogenic cycle of lambda phage) or to cause pulmonary disease (comparable to the lytic cycle of lambda phage). In this latter case, M. tuberculosis kills the host with the aim of achieving transmission to new hosts. Combating the TB epidemic requires stopping transmission. M. bovis BCG, the present vaccine against TB, is derived from M. bovis and only protects against disseminated forms of TB. Thus, a priority in TB research is development of new effective vaccines to prevent pulmonary disease. Attenuated vaccines based on M. tuberculosis as MTBVAC are potential candidates that could contribute to break the TB transmission cycle.

ЛЕТАЛЬНЫЕ ИСХОДЫ У БОЛЬНЫХ ТУБЕРКУЛЕЗОМ В ДИНАМИКЕ ЗА 17 ЛЕТ В КЕМЕРОВСКОЙ ОБЛАСТИ

Lethal outcomes were studied in 704 tuberculosis patients in Kemerovo Region over 2 periods of time: 1995-1997 – 255 cases (including 229 with autopsy) and 2012-2014 – 449 cases (including 413 with autopsy) in three in-patient units of Kemerovo Regional Clinical TB Dispensary (continuous sampling). The number of those died during the second period increased due to co-infection of HIV and tuberculosis. During the second period there was an abrupt increase in disseminated forms of tuberculosis while the number of fibrous-cavernous forms went down, which was due to specific features of tuberculosis in HIV patients given the severe immune deficiency in them. At the same time the increase in the disseminated forms of tuberculosis was detected during the 2nd period in the HIV negative patients.

Tuberculosis

Neuroinfection Update TuberculosisOn March 24, 1882 Robert Koch announced the discovery of the cause of tuberculosis (TB), that day is named the World TB day and its main 2015 year message is that globally every year 9 million people get sick with TB and 3 million people don’t get the care they need. TB is second to HIV/AIDS as the greatest killer worldwide by an infectious agent, and causes one fourth of all HIV-related deaths. In 2013 an estimated 480 000 people developed multidrug resistant TB (MDRTB). A study of 14 years period of all TB cases diagnosed in California found that 9% of patients died during antituberculous therapy and one half of deaths occurred before 60 days of treatment in advanced, meningeal and disseminated forms of TB. Patients treated by private care providers had 3 times increase in risk of death, pointing that public health departments need a strong partnership with private care providers for early detection, adequate treatment and follow up of TB patients. Most cases of MDRTB result from inappropriate drug choice, poor adherence or treatment interruptions. MDRTB is a major challenge for TB eradication and the cost of each new case of MDRTB is 10 to 15 times higher than the cost of treatment of a drug sensitive TB case. All new TB patients need an HIV test and all HIV+ patients need screening for TB. When possible, susceptibility to first-line drugs should be performed in all initial isolates of new TB patients. Neuroinfection Update Tuberculosis On March 24, 1882 Robert Koch announced the discovery of the cause of tuberculosis (TB), that day is named the World TB day and its main 2015 year message is that globally every year 9 million people get sick with TB and 3 million people don’t get the care they need. TB is second to HIV/AIDS as the greatest killer worldwide by an infectious agent, and causes one fourth of all HIV-related deaths. In 2013 an estimated 480 000 people developed multidrug resistant TB (MDRTB). A study of 14 years period of all TB cases diagnosed in California found that 9% of patients died during antituberculous therapy and one half of deaths occurred before 60 days of treatment in advanced, meningeal and disseminated forms of TB. Patients treated by private care providers had 3 times increase in risk of death, pointing that public health departments need a strong partnership with private care providers for early detection, adequate treatment and follow up of TB patients. Most cases of MDRTB result from inappropriate drug choice, poor adherence or treatment interruptions. MDRTB is a major challenge for TB eradication and the cost of each new case of MDRTB is 10 to 15 times higher than the cost of treatment of a drug sensitive TB case. All new TB patients need an HIV test and all HIV+ patients need screening for TB. When possible, susceptibility to first-line drugs should be performed in all initial isolates of new TB patients.

Oral bacillus Calmette-Guérin vaccine against tuberculosis: why not?

The bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine for human use against tuberculosis (TB). Although controversy exists about its efficacy, the BCG vaccine is able to protect newborns and children against disseminated forms of TB, but fails to protect adults against active forms of TB. In the last few years, interest in the mucosal delivery route for the vaccine has been increasing owing to its increased capacity to induce protective immune responses both in the mucosal and the systemic immune compartments. Here, we show the importance of this route of vaccination in newly developed vaccines, especially for vaccines against TB.

Miliary tuberculosis in an immunocompetent male

Introduction: Miliary tuberculosis (tb) is a disseminated form of tuberculosis which may involve the lungs and other organs. It is a rare but potentially lethal form of tuberculosis seen mostly in immunocompromised patients. It is, however, not commonly reported in immunocompetent hosts. case report: We present a case of a 67-year-old African-American male who presented with persistent non-productive cough for three weeks, diarrhea, fatigue and weight loss. there was no history of active tb contacts, HIV infection, or other predisposing factor for immunosuppression. Physical examination was also unremarkable. chest X-ray and computed tomography scan revealed bilateral extensive small nodular infiltrates with negative serial acid-fast sputum smears. Acid-fast bacilli were detected in sputum culture at four weeks and were identified by DNA probe as Mycobacterium tuberculosis. conclusion: Miliary tuberculosis is a potentially lethal form of tuberculosis that mostly affects immunosuppressed patients, although in rare occasions can also affect immunocompetent adults.

The Appropriate DOTS Regimen Greatly Reduces the Disabilities in Polyarticular EPTB

The placement of cases of Extrapulmonary Tuberculosis (EPTB) on the appropriate Directly Observed Treatment Short Course (DOTS) regimen remains a problematic issue in India and often, consultants delay this, leading to significant avoidable pain, discomfort and reduction in the quality of life of the patients. In contrast, a prompt institution of the DOTS regimen can regress such problems, even at a delayed stage. The following case report on polyarticular tuberculosis which involved the bilateral knee and ankle joints without a pulmonary or disseminated form of tuberculosis, amply highlights these facts.

Tuberculosis is a global health issue: challenges and need for new tools

Every year, more than 9 million people are affected by tuberculosis (TB) and 1.8 million die from it. Developing countries are heavily affected. The highest rates per capita are in Africa, but the largest numbers are in Asia, with nearly 60% of the global burden. associated with HIV/AIDS is a huge challenge in Africa and multidrug-resistant (MDR-TB) is frequent in the former USSR and parts of Asia. [1] The United Nations Millennium Development Goal (MDG) related to control aims to halt and begin to reverse the incidence of by 2015, and the STOP Partnership targets elimination of as a major public health problem worldwide by 2050. [2] The World Health Organization (WHO) has developed a six-point Stop Strategy to reach the global targets: (i) pursue high-quality DOTS expansion and enhancement; (ii) address TB/HIV, MDR-TB and other challenges; (iii) contribute to strengthening health systems; (iv) engage all care providers; (v) empower patients with TB; and (vi) enable and promote research. [3] Progress has been made to date toward achieving the global targets. Compared to performance of control programmes in the mid-1990s, up to 6 million human lives have been saved through the implementation of DOTS, later enhanced to the Stop Strategy, since 1995. The global incidence of has peaked in 2004, resulting in an earlier achievement of the MDG related to control. However, the decline since then has been less than 1% per year, which is insufficient to seriously target elimination by 2050. [1] Projections show that, even with the optimization of the current control efforts promoted by the Stop Strategy using the tools available today, efforts will result in an incidence of by 2050 that is much reduced compared to today, but about 100 times higher than the elimination target. Thus, this target cannot be achieved without addressing critical and urgent needs, such as that interrupting transmission focusing on early case detection among vulnerable groups and accelerating innovation for increased access to the best tools available. Furthermore, new tools are needed if elimination is to be targeted assertively. Today in much of the world, the tool most commonly used to diagnose TB, sputum smear microscopy, is more than 100 years old, detects only half of the cases and is often ineffective in diagnosing in people with HIV. Rapid molecular tests for drug resistance, although already available, are not widely available in the field. Drugs for treatment, which are decades old, are not compatible with some anti-retrovirals and the treatments for MDR-TB are lengthy, expensive, and toxic. The only vaccine, Bacillus Calmette-Guerin (BCG), that is more than 85 years old, protects infants from the disseminated forms of TB, but provides unreliable protection against adult pulmonary – the main source of transmission – and, as a result, has had little impact on the global epidemic. Therefore, diagnostics must be developed to provide faster detection of all forms of (smear positive, smear negative, and MDR-TB) and be useable at point of care. They must provide faster results, and be more sensitive and simpler than microscopy to make them useable. Shorter treatment regimens and more effective MDR-TB care regimens are priorities for drug development. An ideal candidate would shorten the treatment from the current six months to less than two months; have a novel mechanism of action; not interact with anti-retrovirals; be taken orally once daily or intermittently; and be low in cost. The vaccine development pipeline, which is focused on both pre and/or post-infection vaccines, is still weak in research needed for clinical trial activation. The priorities to achieve success must include expanding financing for research and development partnerships; attracting more researchers in academia and industry into the research field; fostering more communication between research and implementation communities; and promoting formation of intergovernmental working groups to expand links across neglected critical areas for health research. The constraints include a recent no-growth in financing from Europe and North America for critical research and development [4]; limited incentives for the private sector to engage more broadly; a lack of clinical trial and manufacturing capacity; and limited operational research capacity and financing. A TB Research Movement has been conceived, the goal of which is to stimulate investments, support efforts, accelerate implementation, and expand the existing portfolio across the research continuum to ensure development of those tools that will be conducive to global elimination of by 2050. Its objectives are to provide leadership and advocacy to mobilize increased resources in support of a coherent and comprehensive global research agenda; and to provide a forum for funders and implementers of research to coordinate plans and actions, with the result of ensuring that research needs are addressed, opportunities prioritized, and gaps filled.

Desfecho do tratamento e confirmação laboratorial do diagnóstico de tuberculose em pacientes com HIV/AIDS no Recife, Pernambuco, Brasil

To compare the frequency of unfavorable outcome (death or default and treatment failure) between tuberculosis (TB)/HIV co-infected patients treated for TB after laboratory confirmation of the diagnosis and TB/HIV co-infected patients who were so treated without diagnostic confirmation. A retrospective cohort of TB/HIV co-infected patients who started TB treatment between July of 2002 and June of 2004 at an HIV/AIDS referral center in Recife, Brazil. The main exposure variable, laboratory confirmation of TB, was adjusted for three different sets of variables: sociodemographic variables; HIV/AIDS-related variables; and TB-related variables. In order to evaluate the statistical significance of the results, we calculated odds ratios, with 95% confidence intervals, and p values (from chi-square tests and likelihood ratio tests). A total of 262 patients were studied. No association was found between laboratory confirmation of the diagnosis of TB at treatment outset and unfavorable outcome, even after adjustment for confounders. In the final multiple logistic regression model, the following variables remained: the presence of other opportunistic diseases; CD4 lymphocyte count below 50 cells/mm(3); viral load between 10,000 and 100,000 copies/mL; dyspnea; the disseminated form of TB; and change in the TB treatment regimen due to adverse reactions or intolerance. Our results suggest that TB treatment in TB/HIV co-infected patients without etiologic confirmation of TB, at the discretion of experienced physicians in referral centers, did not increase the risk of unfavorable outcomes. In addition, it allowed the identification of groups that should be closely monitored due to a greater risk of unfavorable outcomes.

Tuberculoses lors de traitements par l’infliximab: Suivi national du 1 er janvier 2000 au 30 juin 2003

Analysis of the tuberculosis cases reported in France in patients treated with infliximab since its marketing approval, assessment of the effect of changes in the summary of product characteristics and national guidelines.Based on tuberculosis reports from the national post-marketing adverse drug reaction databank of the manufacturer from January 1, 2000 through June 30, 2003, and records from the national multicenter retrospective survey on opportunistic infections with anti-TNFalpha, we analyzed all cases of tuberculosis and the impact of the changes made in December 2000 in the summary of product characteristics and the guidelines on the prevention and management of tuberculosis in patients treated with infliximab published in February 2002.56 cases of tuberculosis were reported: the median interval before diagnosis was 12 weeks with a median of 3 infusions. The presence of Koch bacilli was confirmed in 32 patients; 29 patients had extrapulmonary or disseminated forms of tuberculosis. The tuberculosis rate among patients treated with infliximab was greater than among the general population and differed significantly by period (p < 0.005).Tuberculosis can occur within the first 12 weeks of treatment with infliximab. Information for practitioners must be continued, together with surveillance of the tuberculosis cases in France.

Choledocho-enteric fistula due to Mycobacterium tuberculosis in a patient with acquired immunodeficiency syndrome

Intra-abdominal tuberculosis is common in developing countries.1 There is an alarming increase in the number of patients with tuberculosis in the United States and western countries, mostly in patients with acquired immunodeficiency syndrome (AIDS)2 and in new immigrants from endemic areas. Compared with non-immunosuppressed patients, AIDS patients tend to present with the extrapulmonary or disseminated form of tuberculosis. Tuberculosis as the initial manifestation of AIDS was first described among Haitians and intravenous drug users in 1986.3 Since 1987, extrapulmonary tuberculosis with laboratory evidence of HIV infection has been reportable as the AIDS syndrome in the United States according to the Centers for Disease Control and Prevention definition of AIDS. Enteric fistula secondary to intestinal tuberculosis is a recognized complication. We report a patient with AIDS who presented with a choledochoenteric fistula and pneumobilia associated with a retroperitoneal tuberculous abscess.