Protein and Microbial Biomarkers in Sputum Discern Acute and Latent Tuberculosis in Investigation of Pastoral Ethiopian Cohort

Differential diagnosis of tuberculosis (TB) and latent TB infection (LTBI) remains a public health priority in high TB burden countries. Pulmonary TB is diagnosed by sputum smear microscopy, chest X-rays, and PCR tests for distinct Mycobacterium tuberculosis (Mtb) genes. Clinical tests to diagnose LTBI rely on immune cell stimulation in blood plasma with TB-specific antigens followed by measurements of interferon-γ concentrations. The latter is an important cytokine for cellular immune responses against Mtb in infected lung tissues. Sputum smear microscopy and chest X-rays are not sufficiently sensitive while both PCR and interferon-γ release assays are expensive. Alternative biomarkers for the development of diagnostic tests to discern TB disease states are desirable. This study’s objective was to discover sputum diagnostic biomarker candidates from the analysis of samples from 161 human subjects including TB patients, individuals with LTBI, negative community controls (NCC) from the province South Omo, a pastoral region in Ethiopia. We analyzed 16S rRNA gene-based bacterial taxonomies and proteomic profiles. The sputum microbiota did not reveal statistically significant differences in α-diversity comparing the cohorts. The genus Mycobacterium, representing Mtb, was only identified for the TB group which also featured reduced abundance of the genus Rothia in comparison with the LTBI and NCC groups. Rothia is a respiratory tract commensal and may be sensitive to the inflammatory milieu generated by infection with Mtb. Proteomic data supported innate immune responses against the pathogen in subjects with pulmonary TB. Ferritin, an iron storage protein released by damaged host cells, was markedly increased in abundance in TB sputum compared to the LTBI and NCC groups, along with the α-1-acid glycoproteins ORM1 and ORM2. These proteins are acute phase reactants and inhibit excessive neutrophil activation. Proteomic data highlight the effector roles of neutrophils in the anti-Mtb response which was not observed for LTBI cases. Less abundant in the sputum of the LTBI group, compared to the NCC group, were two immunomodulatory proteins, mitochondrial TSPO and the extracellular ribonuclease T2. If validated, these proteins are of interest as new biomarkers for diagnosis of LTBI.

Factors associated with unfavorable outcome of tuberculosis treatment in people deprived of liberty: a systematic review

ABSTRACT Objective: to analyze factors associated with unfavorable outcome of tuberculosis treatment in people deprived of liberty. Method: systematic review, carried out in March 2021 in seven databases, with no delimitation of period of publication. The selection process of publications and data extraction was carried out by two independent reviewers. Results: a total of 1,448 publications was identified and nine were included in the study. Unfavorable outcome was higher among those who were men; had low level of education; were living in a rural area before detention; had longer prison time; received occasional visits; had been transferred between prisons; with no sputum smear microscopy or with a positive result at the diagnosis; with no follow-up sputum smear microscopy, previous history of tuberculosis; having both clinical forms of the disease, HIV/AIDS; alcoholics; smokers; low body weight; and self-administered treatment. Treatment default was associated with young people and death with older people. Conclusion: prison health managers and professionals are expected to establish mechanisms of surveillance and health actions innovation aimed at the population deprived of liberty, making efforts to reduce the unfavorable outcomes of tuberculosis treatment.

Therapeutic itinerary of people with leprosy: paths, struggles, and challenges in the search for care

ABSTRACT Objectives: to understand how the therapeutic itineraries of people affected by leprosy are processed. Methods: this is a descriptive, qualitative study, conducted in April 2018 in Barão de Grajaú in Maranhão, with interviews in the form of narratives of seven patients who had a late leprosy diagnosis. Results: the search for diagnosis is a major difficulty in accessing health services, resulting in a late diagnosis and, consequently, with the presence of visible deformities. It was noticed that the health units do not have a flow, nor protocols for comprehensive treatment, and these people are referred to a referral unit in another state to perform sputum smear microscopy. Final Considerations: leprosy control actions need reformulations that seek the relationship between operational activities, epidemiological indicators and risk factors, in accordance with the real needs of each region, thus highlighting the gaps evidenced in the therapeutic itineraries.

Choosing Wisely: Computed Tomography in the Diagnosis of Adolescents With Intrathoracic Tuberculosis

In a retrospective study of adolescents with intrathoracic tuberculosis (TB), 26 out of the 81 (32%) patients had undergone chest computed tomography (CT). Chest CT was considered unnecessary in 7 (27%), necessary in 7 (27%), and possibly/probably helpful in 12 (46%). Promptly obtaining specimens for sputum smear microscopy, molecular testing, as well as culture for Mycobacterium tuberculosis could avoid several unnecessary CTs.

Protein and Microbial Biomarkers in Sputum Discern Acute and Latent Tuberculosis in Investigation of Pastoral Ethiopian Cohort

Differential diagnosis of tuberculosis (TB) and latent TB infection (LTBI) remains a public health priority in high TB burden countries. Pulmonary TB is diagnosed by sputum smear microscopy, chest X-rays, and PCR tests for distinct Mycobacterium tuberculosis (Mtb) genes. Clinical tests to diagnose LTBI rely on immune cell stimulation in blood plasma with TB-specific antigens followed by measurements of interferon-gamma concentrations. The latter is an important cytokine for cellular immune responses against Mtb in infected lung tissue. Sputum smear microscopy and chest X-rays are not sufficiently sensitive while both PCR and interferon-gamma release assays are expensive. Alternative biomarkers useful for developing diagnostic tests to discern TB disease states are desirable. This study's objective was to discover biomarkers in sputum, assessing the proteomes and microbiomes of 74 TB patients, 46 individuals with LTBI, and 51 negative community controls (NCC). Study participants were from the South Omo province, a pastoral region in southern Ethiopia. A total of 161 and 115 samples were used to determine the 16S rRNA sequence-based bacterial taxonomies and proteomic profiles, respectively. Sputum microbiota did not reveal statistically significant differences in alpha-diversity comparing the three groups. The genus Mycobacterium, representing Mtb, was only identified for the TB group. The latter featured reduced abundance of the genus Rothia in comparison to the LTBI and NCC groups. Rothia is a human respiratory tract commensal and may be sensitive to the inflammatory milieu caused by TB infection. Proteomic data strongly supported innate immune responses against Mtb in subjects with pulmonary TB. Ferritin, an iron storage protein released by damaged host cells, was markedly increased in abundance in TB sputum compared to the LTBI and NCC groups, along with alpha-1-acid glycoproteins ORM1 and ORM2. These proteins are acute phase reactants and inhibit excessive neutrophil activation. Proteomic data also supported effector roles of neutrophils in the anti-Mtb response which was not observed for LTBI cases. Less abundant in sputum of the LTBI group versus the NCC group were two immunomodulatory proteins, mitochondrial TSPO and the extracellular ribonuclease T2. If validated, these proteins are of interest as diagnostic biomarkers for LTBI.

Low Tuberculosis (TB) Case Detection: A Health Facility-Based Study of Possible Obstacles in Kaffa Zone, Southwest District of Ethiopia

Background. In Ethiopia, the national TB case detection rate is becoming improved; still some districts are not able to meet their case detection targets which leads to ongoing spread of TB infections to family members and communities. This study was intended to assess possible obstacles contributing to low TB case detection in Kaffa zone, Southwest Ethiopia. Methods. A cross-sectional descriptive study involving qualitative and quantitative data was conducted from Mar. to Sep. 2019. Sociodemographic characteristics and data on duration of cough, whether sputum smear microscopy was requested or not, and data on TB knowledge and health care-seeking practice were collected from outpatients. Health care delivery barrier for TB case detection was also explored by using in-depth interview and FGD of health staff. Results. From 802 outpatients with coughing for 2 or more weeks of duration, 334 (41.6%) of them were not requested to have TB microscopic diagnosis. Of these, 11/324 (3.4%) of them were positive for TB after sputum smear microscopy. Only 24.2% of the outpatients were aware as they have had health education on TB disease. Twenty-eight percent of patients perceived that TB was due to exposure to cold air, and 13.5% could not mention any sign or symptom of TB. Amazingly, 54.2% of them did not have any information as current TB diagnosis and treatment is free. Thirty-five percent of the patients were taking antibiotics before visiting the health facility. The interrupted supply of TB diagnostic reagents, frequent electricity interruption, shortage of trained TB care providers, weak health information system, and weak active case finding practice were explored as the factors contributing to low TB case detection. Conclusion. Interrupted functioning of diagnostic centers, shortage of trained care providers, limited active TB case finding practice, weak health information system, and inadequate knowledge and health care-seeking practice of the patients were identified as contributors for low TB case detection. Thus, improving functioning of diagnostic centers, active TB case finding activities, and expanding health education on TB disease will help to improve TB case detection in the districts.