Adult Tuberculosis Research Articles

Identification of Respondent Characteristics and Relationship of Clinical Manifestations with Chest Radiograph Lesion in Pulmonary Tuberculosis Patients at Aloei Saboe Hospital

Introduction: Tuberculosis (TB) is an infectious infectious disease caused by Mycobacterium tuberculosis. This study aimed to determine the relationship between clinical manifestations and the results of chest radiographs in adult pulmonary TB patients at Aloei Saboe Hospital.Method: The research design used in this study was cross-sectional by examining the relationship between clinical manifestations and chest radiography results in adult pulmonary TB patients at Aloei Saboe Hospital from October to November 2022. The population of this study was adult pulmonary TB patients using accidental sampling as a sampling technique. The research instrument used was the medical record which contained the patient's anamnesis status and the results of the chest radiography examination. The relationship between variables was then analyzed using the Kolmogorov-Smirnov test.Results: Of the 44 samples, the most common clinical manifestations were dyspnea and chest pain in 12 patients (26.67%). The most chest radiographic results were fibrotic in 21 patients (47.7%). According to the American Thoracic Association (ATA) classification, extensive lesions were predominantly found in 21 patients (47.7%). There was an association between productive cough and chest radiography results (p=0.012). Meanwhile, chest radiographs were not associated with productive cough, hemoptoe, and dyspnea.Conclusion: There is a relationship between productive cough and chest radiography lesions. Further study may determine samples for research that are minimally biased so that the results obtained are more representative of the population.

Prevalence and Associated Factors of Diabetes Mellitus Type 2 Among Tuberculosis Patients in Muscat, Oman, 2017-2020.

Diabetes mellitus (DM) and tuberculosis (TB) are global public health concerns and leading causes of mortality and morbidity worldwide. Coinfection is known to complicate TB control and outcomes. However, there is no national study regarding the prevalence of DM among TB patients in Oman. The objective of the current study was to assess the prevalence of DM and its associated factors among TB patients in Muscat, Oman. We conducted an analytical cross-sectional study using secondary data from the electronic system of the Ministry of Health (Al-Shifa 3+). It includes all adult TB patients in Muscat, from 2017-2020. Sociodemographic data, clinical characteristics, and comorbidities of TB patients were collected. SPSS with 95% CI and p-value ≤ 0.05 was used for statistical analysis. Of 426 TB cases, the prevalence of DM was 27.0%. The associated factors of DM were age group 40-54 years (odds ratio (OR) = 9.08, 95% CI: 4.16-19.84) and ≥ 55 years (OR = 11.35, 95% CI: 5.19-24.82), male (OR = 2.35, 95% CI: 1.45-3.81), being married (OR = 13.18, 95% CI: 4.72-36.84), being employed (OR = 2.30, 95% CI: 1.19-4.47), and Bangladeshi (OR = 7.08, 95% CI: 2.50-20.12) or Indian (OR = 6.14, 95% CI: 2.40-15.70) nationality. The absence of Bacillus Calmette-Guérin scar (OR = 2.06, 95% CI: 1.19-3.56), death (OR = 7.08, 95% CI: 1.26-7.82), and cured after TB treatment (OR = 3.02, 95% CI 1.71-5.31) showed significant association. Also, smoking (OR = 2.93, 95% CI: 1.81-4.76), drinking alcohol (OR = 1.79, 95% CI: 1.10-2.91), hypertension (OR = 10.45, 95% CI: 5.29-20.64), heart disease (OR = 8.50, 95% CI: 1.69-42.77), and renal disease (OR = 4.84, 95% CI: 1.71-13.64) contributed to the study's comorbidities. Old age (adjusted OR = 2.30, 95% CI: 1.72-3.06) and hypertension (adjusted OR = 5.21, 95% CI: 2.28-11.87) were found to be predictors of DM among TB patients. The prevalence of DM among TB patients in Muscat is high. Integrated systematic bidirectional TB-DM screening is needed. Furthermore, special attention is required for associated factors when managing these comorbidities.

Differences in epidemiological and clinical features between adult and pediatric tracheobronchial tuberculosis patients in Southwest China.

Tracheobronchial tuberculosis (TBTB) is a common form of extrapulmonary tuberculosis that affects the tracheobronchial tree. However, the mechanism has not been fully elucidated. Comparisons of clinical characteristics in various age groups can aid in the understanding of TBTB. This retrospective study was conducted at the Public Health Clinical Center of Chengdu between July 2017 and December 2021, including adults and children with TBTB. Clinical data were extracted from medical records. T/T' test, Mann-Whitney U test, Chi-square test, or Fisher's exact test were used in this study. This study enrolled 347 patients with TBTB (175 adults and 172 children). Adult females were more susceptible to TBTB, whereas gender-based differences were not observed in children. Children had a higher occurrence of irritant dry cough and fever, and acute hematogenous disseminated PTB, and specific types of EPTB, but a shorter interval before diagnosis, and lower diagnostic yields compared to adults (P < 0.05). Adults presented more extensive lung lesions and cavitations as compared to children. Granulation hyperplasia and lymph fistula were more frequently observed in children, as well as airway stenosis, but less severe. The study revealed important variations exist in multiple respects between adults and children with TBTB.

The Incidence of Comorbidities in New Adult Tuberculosis Cases

The objective: to determine the potential impact of particular nosologies and their groups on the risk of developing tuberculosis.Subjects and Methods. The incidence of particular nosologies and their groups standardized by gender and age in new tuberculosis cases detected in 2020 was compared to the general incidence of those nosologies among population of RNO-Alania. Relative risk (RR) and statistical significance of differences (p) were determined.Results. RR of type I diabetes mellitus (DM) in tuberculosis patients to the overall incidence of the entire population was 9,5 (p&lt;0,001); RR of viral hepatitis – 6,4 (p&lt;0,001); mental disorders – 3.2 (p&lt;0,001); type II DM – 2,6 (p&lt;0,001); chronic nonspecific lung diseases (CNLD) – 2,3 (p=0,005). There was no excess of RR for digestive diseases (RR=0,9; p=0,9). The role of genitourinary diseases could not be verified due to the lack of observations.

Analisis Faktor Risiko TB paru Anak yang Tinggal Serumah dengan Penderita TB paru Dewasa

Pulmonary tuberculosis (TB) is still a major public health problem in Indonesia. Based on the Household Health Survey (SKRT) results tuberculosis is the number one respiratory disease and infectious disease. Tuberculosis in children causes growth disorders and even death. If pulmonary tuberculosis in a child is not treated immediately, it can quickly develop into parenchymal or tubercular pneumonia, milliary tuberculosis, bone tuberculosis (scrofuloderma), joint tuberculosis, abdominal tuberculosis, and even meningitis. This study used a case-control design with analytical observation. Children who were exposed to and lived in the same household with adult pulmonary tuberculosis patients as many as 90 adults participated in the study. The case sample consisted of children aged 0-15 years who were diagnosed with Pulmonary TB by doctors at the Wania Health Center, Mimika Regency. The case sample size was 30 respondents and the control sample was 30 respondents. The free variables in this study were parental knowledge, BCG vaccination history, child nutritional status, occupancy density, the behavior of TB sufferers at home, and length of contact. Data were analyzed using univariate analysis, bivariate analysis, and multivariate analysis (multiple logistic regression). The results of the study analysis showed that the factors that influence the incidence of tuberculosis in children are parental knowledge (p = 0.001), BCG vaccination history (p = 0.001), and the behavior of adult tuberculosis sufferers in the household (p = 0.000) The conclusion of the study was that the behavior of adult pulmonary tuberculosis patients who lived in the same house with children was most influential in the transmission of pulmonary tuberculosis in children who lived in the same household as adult pulmonary tuberculosis patients at the Health Centre of Wania, Mimika District.

Xpert MTB/RIF Ultra Assay Using Stool: an Effective Solution for Bacilli Identification from Adult Pulmonary Tuberculosis Suspects without Expectorated Sputum.

This study evaluated the diagnostic performance of stool-based Xpert MTB/RIF Ultra assay (Xpert-Ultra, Cepheid, USA) against other tests using respiratory tract specimens (RTS) and stool for diagnosing adult pulmonary tuberculosis. A prospective study on patients with presumptive pulmonary tuberculosis was conducted in Beijing Chest Hospital from June to November 2021. The smear test, MGIT960 liquid culture, and Xpert MTB/RIF (Xpert, Cepheid, USA) were performed simultaneously on RTS, and smear, culture Xpert, and Xpert-Ultra were performed simultaneously using stool. Patients were grouped based on the outcomes of RTS examination and other tests. In total, 130 eligible patients were enrolled that included 96 pulmonary tuberculosis and 34 non-TB patients. The sensitivity of smear, culture, Xpert, and Xpert-Ultra using stool was 10.96%, 23.28%, 60.27%, and 79.45%, respectively. The specificities of Xpert and Xpert-Ultra using RTS and stool were all 100% (34/34). Notably, all five confirmed cases detected by bronchoalveolar lavage fluid (BALF) examination yielded Xpert-Ultra positive outcomes with the stool specimens. Xpert-Ultra assay on stool sample harbors comparable sensitivity with Xpert on RTS. Thus, the Xpert-Ultra testing on stool specimens could be a very promising and practical strategy to improve pulmonary tuberculosis (PTB) diagnosis, especially among patients who could not expectorate sputum. IMPORTANCE This study is aimed at assessing the value of Xpert MTB/RIF Ultra (Xpert-Ultra) in PTB on stool in adult in low HIV settings and Xpert-Ultra assay on stool sample harboring comparable sensitivity with Xpert MTB/RIF on respiratory tract specimens. Although the yield in stool samples by Xpert-Ultra is lower than RTS, it may be useful in detecting disease in presumptive TB patients who cannot expectorate sputum and are not open to BALF collection. In addition, Xpert-Ultra with a "trace call" on stool in adult was highly supportive of PTB.

Ethambutol and visual assessment in England: current practice and recommendations.

Standard treatment for tuberculosis (TB) in children and adults includes an initial two-month course of ethambutol, a drug that in rare cases can cause optic neuropathy and irreversible vision loss. There is a lack of clear guidance on what vision assessments are needed before and during treatment with ethambutol, with the Royal College of Ophthalmologists, National Institute for Health and Care Excellence, British National Formulary and British Thoracic Society offering different guidance. We aimed to assess how vision is routinely tested in patients treated with ethambutol in TB services across England. An online survey developed by Public Health England was sent to all TB services in England in 2018 to assess current practice and inform the development of best practice recommendations for visual assessment of patients treated with ethambutol for TB. Sixty-six TB professionals from across England responded, a response rate of 54%. The results showed variations in practice, including when to omit ethambutol from treatment, the timing and frequency of visual assessment, the type of visual assessment, referral processes and management of visual changes. This national survey highlights the need for clear guidelines on the testing of vision for patients taking ethambutol at recommended doses, before and during treatment. We suggest a pragmatic approach to visual assessment to reduce variation in practice, proposing a stepwise pathway for patients on standard TB treatment for local adaptation.

T-BACCO SCORE: A predictive scoring tool for tuberculosis (TB) loss to follow-up among TB smokers.

Loss to follow-up (LTFU) and smoking during TB treatment are major challenges for TB control programs. Smoking increases the severity and prolongs TB treatment duration, which lead to a higher rate of LTFU. We aim to develop a prognostic scoring tool to predict LTFU among TB patients who smoke to improve successful TB treatment outcomes. The development of the prognostic model utilized prospectively collected longitudinal data of adult TB patients who smoked in the state of Selangor between 2013 until 2017, which were obtained from the Malaysian Tuberculosis Information System (MyTB) database. Data were randomly split into development and internal validation cohorts. A simple prognostic score (T-BACCO SCORE) was constructed based on the regression coefficients of predictors in the final logistic model of the development cohort. Estimated missing data was 2.8% from the development cohort and was completely at random. Model discrimination was determined using c-statistics (AUCs), and calibration was based on the Hosmer and Lemeshow goodness of fit test and calibration plot. The model highlights several variables with different T-BACCO SCORE values as predictors for LTFU among TB patients who smoke (e.g., age group, ethnicity, locality, nationality, educational level, monthly income level, employment status, TB case category, TB detection methods, X-ray categories, HIV status, and sputum status). The prognostic scores were categorized into three groups that predict the risk for LTFU: low-risk (<15 points), medium-risk (15 to 25 points) and high-risk (> 25 points). The model exhibited fair discrimination with a c-statistic of 0.681 (95% CI 0.627-0.710) and good calibration with a nonsignificant chi-square Hosmer‒Lemeshow's goodness of fit test χ2 = 4.893 and accompanying p value of 0.769. Predicting LTFU among TB patients who smoke in the early phase of TB treatment is achievable using this simple T-BACCO SCORE. The applicability of the tool in clinical settings helps health care professionals manage TB smokers based on their risk scores. Further external validation should be carried out prior to use.

Drivers of sex differences in the South African adult tuberculosis incidence and mortality trends, 1990–2019

Males have higher tuberculosis incidence and mortality rates than females. This study aimed to assess how sex differences in tuberculosis incidence and mortality could be explained by sex differences in HIV, antiretroviral treatment (ART) uptake, smoking, alcohol abuse, undernutrition, diabetes, social contact rates, health-seeking patterns, and treatment discontinuation. We developed an age-sex-stratified dynamic tuberculosis transmission model and calibrated it to South African data. We estimated male-to-female (M:F) tuberculosis incidence and mortality ratios, the effect of the abovementioned factors on the M:F ratios and PAFs for the tuberculosis risk factors. Over the period 1990–2019, the M:F ratios for tuberculosis incidence and mortality rates persisted above 1.0, and the figures reached 1.70 and 1.65, respectively, by the end of 2019. In 2019, HIV contributed greater increases in tuberculosis incidence among females than males (54.5% vs. 45.6%); however, females experienced more reductions due to ART than males (38.3% vs. 17.5%). PAFs for tuberculosis incidence due to alcohol abuse, smoking, and undernutrition, in men were 51.4%, 29.5%, and 16.1%, respectively, higher than females (30.1%, 15.4%, and 10.7%, respectively); the PAF due to diabetes was higher in females than males (22.9% vs. 17.5%). Lower health-seeking rates in males accounted for a 7% higher mortality rate in men. The higher burden of tuberculosis in men highlights the need to improve men’s access to routine screening and ensure earlier diagnosis. Sustained efforts in providing ART remain critical in reducing HIV-associated tuberculosis. Additional interventions to reduce alcohol abuse and tobacco smoking are also needed.

Long-Term Intake of Linezolid Elevates Drug Exposure and Reduces Drug Clearance and Elimination in Adults With Drug-Resistant Pulmonary Tuberculosis.

Pharmacokinetic (PK) studies are critical for dose optimization, and there is a paucity of linezolid (LZD) PK data for prolonged use in drug-resistant tuberculosis (DR-TB). Therefore, the authors evaluated the pharmacokinetics of LZD at two-time intervals in DR-TB during long-term use. PK evaluation of LZD was performed at the end of the 8th and 16th weeks of treatment in a randomly selected subset of adult pre-extensively drug-resistant pulmonary tuberculosis patients (n = 18) from a multicentric interventional study (Building Evidence to Advance Treatment of TB/BEAT study; CTRI/2019/01/017310), wherein a daily dose of 600 mg LZD was used for 24 weeks. Plasma LZD levels were measured using a validated high-pressure liquid chromatography (HPLC) method. The LZD median plasma C max was comparable between the 8th and 16th weeks [18.3 mg/L, interquartile range (IQR: 15.5-20.8 and 18.8 mg/L, IQR: 16.0-22.7, respectively)]. However, the trough concentration increased significantly in the 16th week (3.16 mg/L, IQR: 2.30-4.76), compared with the 8th week (1.98 mg/L, IQR: 0.93-2.75). Furthermore, compared with the 8th week, in the 16th week, there was a significant increase in drug exposure (AUC 0-24 = 184.2 mg*h/L, IQR: 156.4-215.8 versus 233.2 mg*h/L, IQR: 187.9-277.2), which corroborated with a longer elimination half-life (6.94 hours, IQR: 5.55-7.99 versus 8.47 hours, IQR:7.36-11.35) and decreased clearance (2.91 L/h, IQR: 2.45-3.33 versus 2.19 L/h, IQR: 1.49-2.78). Long-term daily intake of 600 mg LZD resulted in a significant elevation in trough concentration (>2.0 mg/L) in 83% of the study participants. Furthermore, increased LZD drug exposure may be partly because of decreased clearance and elimination. Overall, the PK data underscore the need for dose adjustment when LZDs are intended for long-term treatment.

Prevalence of Stigma Among TB Patients and Its Associated Factors - A Community Based Cross-Sectional Study in Puducherry, India

Background: Tuberculosis (TB) is a disease that has both medical as well as social dimensions. Stigma and associated discrimination experienced by persons affected by TB is a barrier to the interventions towards TB elimination. A better understanding of stigma will improve the effectiveness of the interventions aimed to alleviate the effects of TB stigma. The objectives were to measure the prevalence of self, anticipated, experienced stigma and its associated factors and to explore the impact of tuberculosis related stigma among TB patients. Methodology: A cross-sectional study was conducted in Puducherry district, Southern India among 420 adult drug sensitive non-HIV TB patients registered under NTEP. Data was collected by face-to-face interview using standardised questionnaire. Results: The mean(±SD) age of the study participants was 44.5 (±15.03) years. Majority were males (267, 63.6%) and were married (330, 78.6%). The prevalence of stigma among TB patients was found to be 69.3%. Perceived stigma was noted in 47.1%, 33.6% had self- stigma and 26.0% had experienced stigma. On measuring the impact of stigma, 52.6% reported participation restriction. Illiteracy and lower-socio economic status were found to be significantly associated with TB stigma. Conclusions: Stigma among TB patients was high. Tailored patient-centric interventions to address stigma and discrimination using culturally appropriate and locally available resources are necessary.

CO-INFECTION WITH HERPESVIRUSES AS A NEW ASPECT OF TUBERCULOSIS IN CHILDREN

The increase in the incidence of tuberculosis in adults in recent years leads to negative changes in the epidemiological situation among children. Tuberculosis infection is often found against the background of various chronic pathologies. It has been established that the activation of opportunistic, especially herpetic, infections increases the risk of infection with MBT. Tuberculosis, in turn, has a clinically more severe course against the background of secondary immunodeficiency. In childhood, the immaturity of the immune system is added, which in turn can also serve as a prerequisite for the progression of the tuberculosis process. A so-called vicious circle is formed - a persistent, latent herpes infection leads to the appearance of an immunodeficiency state, in turn, mycobacterium tuberculosis – contributes to the further deepening of immunological dysfunction, which leads to the development of the syndrome of violation of anti-infective protection and creates the basis for the progression of the tuberculosis process. Currently, the actual goal of scientific research is to establish the specific weight of herpesvirus infections among tuberculosis patients, their impact on the occurrence, spread and course of various forms of tuberculosis, the study of virological, immunological and clinical-epidemiological aspects of the problem of co-infection of tuberculosis and herpesviruses. The resolution of the issue of combined infection as a new aspect of tuberculosis can play a decisive role in the effective diagnosis and prediction of the severity of the course of tuberculosis in childhood at the current stage and will improve the epidemiological situation with tuberculosis in general.

Burden of Pulmonary Rifampicin-Resistant Tuberculosis in Kajiado, Kenya: An Observational Study.

Rifampicin resistance (RR) is a major challenge in the clinical management of tuberculosis (TB), but data on its prevalence are still sparse in many countries. Our study aimed at estimating the prevalence of RR-TB in Kajiado County, Kenya. Secondary objectives were to estimate the incidence of pulmonary TB in adults and the rate of HIV-TB coinfection. We conducted an observational study in the context of the ATI-TB Project, carried out in Kajiado. The project was based on an active-case-finding campaign implemented with the aid of village chiefs, traditional healers and community health volunteers. Diagnosis relied on Xpert MTB/RIF, including a mobile machine that could be used to cover areas where testing would otherwise be difficult. In sum, 3840 adults were screened for active TB during the campaign. RR cases among all TB diagnoses were 4.6%. The annual incidence of pulmonary TB among adults was 521 cases per 100,000 population. The rate of HIV coinfection was 22.2% among pulmonary TB diagnoses. The prevalence of RR-TB was four times that what could be inferred from official notifications in Kajiado, and higher than overall prevalence in Kenya. In addition, our estimate of incidence of pulmonary TB in adults in Kajiado significantly differed from cases notified in the same area. In contrast, the rate of HIV coinfection was in line with national and regional data. TB diagnostic capability must be strengthened in Kajiado to improve patients' management and public health interventions.

Loss to follow-up tuberculosis treatment and associated factors among adults attending at public health facilities in Warder District, Somali Regional State, Eastern Ethiopia.

Tuberculosis is a major public health problem worldwide, particularly in resource-limited countries. Loss of follow-up during treatment is one of the major obstacles in the fight against tuberculosis, which has serious implications for patients, their families, communities, and health service providers. To assess the magnitude of the loss to follow-up tuberculosis treatment and associated factors among adults attending public health facilities in Warder District, Somali Regional State, eastern Ethiopia from November 02-17, 2021. A 5-year (from 1 January 2016 to 31 December 2020) retrospective study was conducted on 589 adult tuberculosis treatment records. Data were collected using a structured data extraction format. Data were analyzed using STATA version 14.0 statistical package. Variables with P < 0.05 in the multivariate logistic regression analysis were considered statistically significant. A total of 98 (16.6%) TB patients failed to follow up with their treatment. Age between 55 and 64 years (AOR = 4.4, 95% CI: 1.9-9.9), being male (AOR = 1.8, 95% CI: 1.1-2.9), living more than 10 km away from a public health facility (AOR = 4.9, 95% CI:2.5-9.4), and having a history of tuberculosis treatment (AOR = 2.3, 95% CI: 1.2-4.4) were associated with a higher likelihood of not following up, while having a positive initial smear result (AOR = 0.48, 95% CI: 0.24-0.96) was associated with a lower probability of not following up. One out of six patients was lost to follow-up after initiating their tuberculosis treatment. Hence, improving the accessibility of public health facilities with a special focus on older adults, male patients, smear-negative patients, and retreatment cases is highly warranted among TB patients.

Prevalence and Impact of Diabetes Mellitus in Adult Tuberculosis Patients;A Cross-Sectional Study

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Lupus vulgaris on face: a case report

Lupus vulgaris is the most common form of cutaneous tuberculosis in adults. Starts either by re-infection or by lymphatic or hematogenous spread or by direct spread in individuals with moderate immunity and high degree of tuberculin sensitivity. Females affected 2-3 times more, constitute 1-2% of all extra-pulmonary TB. Common sites involved are face and neck. We reported a case lupus vulgaris in a 52 year old female patient.

Comparative serum lipid and immunohematological values among adult pulmonary tuberculosis and tuberculosis lymphadenitis cases and their association with sputum bacilli load and time to culture positivity in Northwestern Ethiopia

BackgroundThe serum lipid and immunohematological values of tuberculosis lymphadenitis (TBLN) patients is poorly documented relative to pulmonary tuberculosis (PTB) cases. Therefore, the aim of this study was to investigate the serum lipid and immunohematological values of patients with TBLN in comparison with PTB (PTB) patients.MethodsAn institution-based comparative cross-sectional study was conducted in Northwest Ethiopia from March to December 2021. The study participants were bacteriologically confirmed PTB (n = 82) and TBLN (n = 94) cases with no known comorbidity and whose ages was greater than 18 years and with no current pregnancy. Independent sample t-test, one-way ANOVA, box plot, and correlation matrix were used to analyze the data.ResultsThe body mass index (BMI), CD4 + T cell count, and high-density lipoprotein-Cholesterol (HDL-C) values were significantly higher among TBLN cases compared with PTB cases. Additionally, the total white blood cell (WBC) count, hemoglobin (Hb), total Cholesterol (CHO) and creatinine (Cr) values were relatively higher among TBLN than PTB (P > 0.05). On the reverse, the platelet count and triacylglycerol (TAG) values were relatively higher among PTB than in TBLN cases. While the mean days of culture positivity were 11.6 days for TBLN, the mean days of culture positivity were 14.0 days for PTB. Anemia and serum lipid values showed no correlation with sputum bacilli load and time to culture positivity.ConclusionTuberculous lymphadenitis patients were well-endowed with serum lipid, immunological and nutritional status compared with PTB cases. Hence, the high incidence rate of TBLN in Ethiopia could not be explained by low peripheral immunohematological values, malnutrition, Anemia, and dyslipidemia. Further study for identifying the predictors for TBLN in Ethiopia is highly desirable.

Impact of Community-Wide Tuberculosis Active Case Finding and Human Immunodeficiency Virus Testing on Tuberculosis Trends in Malawi.

Tuberculosis case-finding interventions are critical to meeting World Health Organization End TB strategy goals. We investigated the impact of community-wide tuberculosis active case finding (ACF) alongside scale-up of human immunodeficiency virus (HIV) testing and care on trends in adult tuberculosis case notification rates (CNRs) in Blantyre, Malawi. Five rounds of ACF for tuberculosis (1-2 weeks of leafleting, door-to-door enquiry for cough and sputum microscopy) were delivered to neighborhoods ("ACF areas") in North-West Blantyre between April 2011 and August 2014. Many of these neighborhoods also had concurrent HIV testing interventions. The remaining neighborhoods in Blantyre City ("non-ACF areas") provided a non-randomized comparator. We analyzed TB CNRs from January 2009 until December 2018. We used interrupted time series analysis to compare tuberculosis CNRs before ACF and after ACF, and between ACF and non-ACF areas. Tuberculosis CNRs increased in Blantyre concurrently with start of ACF for tuberculosis in both ACF and non-ACF areas, with a larger magnitude in ACF areas. Compared to a counterfactual where pre-ACF CNR trends continued during ACF period, we estimated there were an additional 101 (95% confidence interval [CI] 42 to 160) microbiologically confirmed (Bac+) tuberculosis diagnoses per 100 000 person-years in the ACF areas in 3 and a half years of ACF. Compared to a counterfactual where trends in ACF area were the same as trends in non-ACF areas, we estimated an additional 63 (95% CI 38 to 90) Bac + diagnoses per 100 000 person-years in the same period. Tuberculosis ACF was associated with a rapid increase in people diagnosed with tuberculosis in Blantyre.

A novel multi-component protein vaccine ECP001 containing a protein polypeptide antigen nPstS1 riching in T-cell epitopes showed good immunogenicity and protection in mice.

Tuberculosis (TB) is an infectious disease that seriously affects human health. Until now, the only anti-TB vaccine approved for use is the live attenuated Mycobacterium bovis (M. bovis) vaccine - BCG vaccine, but its protective efficacy is relatively low and does not provide satisfactory protection against TB in adults. Therefore, there is an urgent need for more effective vaccines to reduce the global TB epidemic. In this study, ESAT-6, CFP-10, two antigens full-length and the T-cell epitope polypeptide antigen of PstS1, named nPstS1, were selected to form one multi-component protein antigens, named ECP001, which include two types, one is a mixed protein antigen named ECP001m, the other is a fusion expression protein antigen named ECP001f, as candidates for protein subunit vaccines. were prepared by constructing one novel subunit vaccine by mixing or fusing the three proteins and combining them with aluminum hydroxide adjuvant, and the immunogenicity and protective properties of the vaccine was evaluated in mice. The results showed that ECP001 stimulated mice to produce high titre levels of IgG, IgG1 and IgG2a antibodies; meanwhile, high levels of IFN-γ and a broad range of specific cytokines were secreted by mouse splenocytes; in addition, ECP001 inhibited the proliferation of Mycobacterium tuberculosis in vitro with a capacity comparable to that of BCG. It can be concluded that ECP001 is a novel effective multicomponent subunit vaccine candidate with potential as BCG Initial Immunisation-ECP001 Booster Immunisation or therapeutic vaccine for M. tuberculosis infection.

Undiagnosed Pulmonary Tuberculosis (TB) and Coronavirus Disease 2019 (COVID-19) in Adults Dying at Home in a High-TB-Burden Setting, Before and During Pandemic COVID-19: An Autopsy Study.

Missing or undiagnosed patients with tuberculosis (TB) or coronavirus disease 2019 (COVID-19) are of concern. Identifying both infections in patients with no diagnosis prior to death contributes to understanding the burden of disease. To confirm reports of global reduction in TB incidence, a 2012 autopsy study of adults dying at home of natural causes in a high-TB-burden setting was repeated, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assessments after the first COVID-19 surge in South Africa. Adult decedents who died at home with insufficient information to determine cause of death, no recent hospitalization, and no current antemortem TB or COVID-19 diagnosis were identified between March 2019 and October 2020 with a 4-month halt during lockdown. A standardized verbal autopsy followed by minimally invasive needle autopsy (MIA) was performed. Biopsies were taken for histopathology from liver, bilateral brain and lung; bronchoalveolar lavage fluid was collected for Xpert (MTB/RIF) and mycobacterial culture, and blood for human immunodeficiency virus (HIV) polymerase chain reaction (PCR) testing. After the start of the COVID-19 pandemic, a nasopharyngeal swab and lung tissue were subjected to SARS-CoV-2 PCR testing. Sixty-six MIAs were completed in 25 men and 41 women (median age, 60 years); 68.2% had antemortem respiratory symptoms and 30.3% were people with HIV. Overall, TB was diagnosed in 11 of 66 (16.7%) decedents, and 14 of 41 (34.1%) in the COVID-19 pandemic were SARS-CoV-2 positive. Undiagnosed TB in adults dying at home has decreased but remains unacceptably high. Forty percent of decedents had undiagnosed COVID-19, suggesting that estimates of excess deaths may underestimate the impact of SARS-CoV-2 on mortality.