Predictors of active pulmonary tuberculosis among hospitalized patients with atypical symptom and sign and underlying diseases having impact on the outcome of the COVID-19 (preprint)

Background This study aimed to focus on the diagnostic use of high-resolution computed tomography (HRCT) to identify active pulmonary tuberculosis (aPTB) with atypical symptom and sign among the hospitalized patients with the underlying diseases having the impact on the outcome of the Coronavirus disease 2019 (COVID-19).Methods Within the study period (2018.01.01-2021.12.31), for patients with underlying diseases having the impact on the outcome of the COVID-19, chest –x-ray (CXR) / HRCT scans along with their patients’ charts were reviewed. These patients (n = 4,380) were classified into the [aPTB] group I (G1, n = 277) and pulmonary disease without aPTB (G2, n = 4103). Lung morphology, and lobar (segmental) distribution using CXR/HRCT, the underlying diseases and clinical symptom/sign were analyzed. To identify independent variables associated with G1, multivariate analysis was performed. Independent variables were used to generate prediction scores, which were used to develop models for predicting G1.Results For the HRCT model, multivariate analysis revealed cavitation, clusters nodules/mass (CNM) of the right/left upper lobe or ground-glass opacity were useful predictors for the G1. The negative predictive value of the HRCT model, and the CNM model for the GI were 99.3%, and 97.5%, respectively. However, the CNM model has the highest positive predictive value of 95.4%.Conclusions The CNM model may play an auxiliary role for the identification of G1 with atypical symptom and sign among the patients with underlying diseases having the impact on the outcome of the COVID-19.

The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication (preprint)

SARS-CoV-2 infection leads to vastly divergent clinical outcomes ranging from asymptomatic infection to fatal disease. Co-morbidities, sex, age, host genetics and vaccine status are known to affect disease severity. Yet, how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure impacts the control of viral replication remains poorly understood. We demonstrate here that immune events in the mouse lung closely preceding SARS-CoV-2 infection significantly impact viral control and we identify key innate immune pathways required to limit viral replication. A diverse set of pulmonary inflammatory stimuli, including resolved antecedent respiratory infections with S. aureus or influenza, ongoing pulmonary M. tuberculosis infection, ovalbumin/alum-induced asthma or airway administration of defined TLR ligands and recombinant cytokines, all establish an antiviral state in the lung that restricts SARS-CoV-2 replication upon infection. In addition to antiviral type I interferons, the broadly inducible inflammatory cytokines TNF and IL-1 precondition the lung for enhanced viral control. Collectively, our work shows that SARS-CoV-2 may benefit from an immunologically quiescent lung microenvironment and suggests that heterogeneity in pulmonary inflammation that precedes or accompanies SARS-CoV-2 exposure may be a significant factor contributing to the population-wide variability in COVID-19 disease outcomes.

Stool Xpert MTB/RIF as a possible diagnostic alternative to sputum in Africa: a systematic review and meta-analysis.

Introduction: Worldwide, COVID-19 pandemic lead to a large fall in the number of newly reported TB cases. In sub-Saharan Africa, microbiological diagnosis of TB is generally based on smear microscopy and Xpert MTB/RIF on sputum samples, but good quality sputum samples are often difficult to obtain, leading clinicians to rely on more invasive procedures for diagnosis. Aim of this study was to investigate pooled sensitivity and specificity of Xpert MTB/RIF on stool samples compared to respiratory microbiological reference standards in African countries. Methods: Four investigators independently searched PubMed, SCOPUS, and Web of Science until 12th October 2022, then screened titles and abstracts of all potentially eligible articles. The authors applied the eligibility criteria, considered the full texts. All the studies reported the data regarding true positive (TP), true negative (TN), false positive (FP) and false negative (FN). Risk of bias and applicability concerns were assessed with the Quadas-2 tool. Results: overall, among 130 papers initially screened, we evaluated 47 works, finally including 13 papers for a total of 2,352 participants, mainly children. The mean percentage of females was 49.6%, whilst the mean percentage of patients reporting HIV was 27.7%. Pooled sensitivity for Xpert MTB/RIF assay for detecting pulmonary tuberculosis was 68.2% (95%CI: 61.1-74.7%) even if characterized by a high heterogeneity (I2=53.7%). Specificity was almost 100% (99%, 95%CI: 97-100%; I2 = 45.7%). When divided for reference standard, in the six studies using sputum and nasogastric aspirate the accuracy was optimal (AUC = 0.99, SE = 0.02), whilst in the studies using only sputum for tuberculosis detection the AUC was 0.85 (with a SE = 0.16). The most common source of bias was exclusion of enrolled patients in the analysis. Conclusions: Our study confirms that, in Africa, stool Xpert MTB/RIF may be a useful rule-in test for children above and below 5 years of age under evaluation for pulmonary tuberculosis. Sensitivity increased substantially when using both sputum and nasogastric aspirate as reference samples.

Beneficial or detrimental activity of regulatory T cells, indoleamine 2,3-dioxygenase, and heme oxygenase-1 in the lungs is influenced by the level of virulence of Mycobacterium tuberculosis strain infection.

Tuberculosis (TB) caused by the complex Mycobacterium tuberculosis (Mtb) is the main cause of death by a single bacterial agent. Last year, TB was the second leading infectious killer after SARS-CoV-2. Nevertheless, many biological and immunological aspects of TB are not completely elucidated, such as the complex process of immunoregulation mediated by regulatory T cells (Treg cells) and the enzymes indoleamine 2,3-dioxygenase (IDO) and heme oxygenase 1 (HO-1). In this study, the contribution of these immunoregulatory factors was compared in mice infected with Mtb strains with different levels of virulence. First Balb/c mice were infected by intratracheal route, with a high dose of mild virulence reference strain H37Rv or with a highly virulent clinical isolate (strain 5186). In the lungs of infected mice, the kinetics of Treg cells during the infection were determined by cytofluorometry and the expression of IDO and HO-1 by RT-PCR and immunohistochemistry. Then, the contribution of immune-regulation mediated by Treg cells, IDO and HO-1, was evaluated by treating infected animals with specific cytotoxic monoclonal antibodies for Treg cells depletion anti-CD25 (PC61 clone) or by blocking IDO and HO-1 activity using specific inhibitors (1-methyl-D,L-tryptophan or zinc protoporphyrin-IX, respectively). Mice infected with the mild virulent strain showed a progressive increment of Treg cells, showing this highest number at the beginning of the late phase of the infection (28 days), the same trend was observed in the expression of both enzymes being macrophages the cells that showed the highest immunostaining. Animals infected with the highly virulent strain showed lower survival (34 days) and higher amounts of Treg cells, as well as higher expression of IDO and HO-1 one week before. In comparison with non-treated animals, mice infected with strain H37Rv with depletion of Treg cells or treated with the enzymes blockers during late infection showed a significant decrease of bacilli loads, higher expression of IFN-g and lower IL-4 but with a similar extension of inflammatory lung consolidation determined by automated morphometry. In contrast, the depletion of Treg cells in infected mice with the highly virulent strain 5186 produced diffuse alveolar damage that was similar to severe acute viral pneumonia, lesser survival and increase of bacillary loads, while blocking of both IDO and HO-1 produced high bacillary loads and extensive pneumonia with necrosis. Thus, it seems that Treg cells, IDO and HO-1 activities are detrimental during late pulmonary TB induced by mild virulence Mtb, probably because these factors decrease immune protection mediated by the Th1 response. In contrast, Treg cells, IDO and HO-1 are beneficial when the infection is produced by a highly virulent strain, by regulation of excessive inflammation that produced alveolar damage, pulmonary necrosis, acute respiratory insufficiency, and rapid death.

Tuberculosis in Poland in 2020.

AIM OF THE STUDY: To evaluate the main features of epidemiology of tuberculosis (TB) in 2020 in Poland and to compare with the situation in the European Union and European Economic Area (EU/EEA) countries. MATERIAL AND METHODS: Analysis of case-based data on TB patients from National TB Register, data on anti-TB drug susceptibility in cases notified in 2020, data from Statistics Poland on deaths from tuberculosis in 2019, data from National Institute of Public Health NIH - National Research Institute (NIPH NIH - NRI) on HIV-positive subjects for whom TB was an AIDS-defining disease, data from the report "European Centre for Disease Prevention and Control, WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2022 - 2020 data. Copenhagen: WHO Regional Office for Europe and Stockholm: European Centre for Disease Prevention and Control; 2022." RESULTS: In 2020, 3,388 TB cases were reported in Poland. The incidence rate was 8.8 cases per 100,000 with large variability between voivodeships from 5.5 to 13.3 per 100,000. A decrease in the incidence was found in 15 voivodeships, the most significant in Slaskie voivodship (63.9%). The number of all pulmonary tuberculosis cases was 3,237 i.e. 8.4 per 100,000. Pulmonary cases represented 95.5% of all TB cases. In 2020, 151 extrapulmonary TB cases were notified (4.5% of all TB cases). Pulmonary tuberculosis was bacteriologically confirmed in 2,573 cases (79.5% of all pulmonary TB cases, the incidence rate 6.7 per 100,000). The number of smear-positive pulmonary TB cases was 1,771 i.e. 4.6 per 100,000 (54.7% of all pulmonary TB cases). In 2020, there were 38 cases (15 of foreign origin) with multidrug resistant TB (MDR-TB) representing 1.6% of cases with known drug sensitivity. The incidence rates of tuberculosis were growing along with increasing age from 0.7 per 100,000 among children (0-14 years) to 15.0 per 100,000 among subjects in the age group 45-64 years, the incidence rate in the age group ≥65 years was 12.1 per 100,000. There were 39 cases in children up to 14 years of age (1.2% of the total) and 49 cases in adolescents between 15 and 19 years of age - rates 0.7 and 2.7 per 100,000 respectively. In 2020, there were 2,506 cases of tuberculosis in men and 882 in women. The TB incidence in men - 13.5 per 100,000 was 3.0 times higher than among women - 4.5. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 50-54 years - 26.8 vs. 4.1 and in age group 55 to 59 years - 28.7 vs. 4.8. In 2020, there were 116 patients of foreign origin among all cases of tuberculosis in Poland (3.4%). In 2019, TB was the cause of death for 456 people (mortality rate - 1.2 per 100,000). CONCLUSIONS: TB incidence in Poland in 2020 was 36.7% lower than in 2019. Such significant declines in the incidence have not been observed in the last two decades. As in previous years, there were differences in incidence rates between voivodeships with an unexpectedly sharp decrease in incidence in Silesia (Slaskie voivodeship). The percentage of tuberculosis cases with bacteriological confirmation exceeded 78%, more than in EU/EEA countries (67.3%). The percentage of MDR-TB cases was still lower than the average in EU/EEA countries (1.6% vs. 3.8%). The highest incidence rates were found in Poland in the older age groups (EU/EEAaged 25 to 44). The percentage of children up to 14 years of age among the total number of TB patients was 1.2%, less than the average in EU/EEA countries (3.8%). The incidence of tuberculosis in men was three times higher than in women in Poland, and six times higher in patients aged 50 to 59. The impact of migration on the TB pattern in Poland has not yet become significant in 2020. The percentage of foreigners among TB patients was 3.4% (33% in EU/EEA countries).

In silico EsxG EsxH rational epitope selection: Candidate epitopes for vaccine design against pulmonary tuberculosis.

Rational design of new vaccines against pulmonary tuberculosis is imperative. Early secreted antigens (Esx) G and H are involved in metal uptake, drug resistance, and immune response evasion. These characteristics make it an ideal target for rational vaccine development. The aim of this study is to show the rational design of epitope-based peptide vaccines by using bioinformatics and structural vaccinology tools. A total of 4.15 µs of Molecular Dynamics simulations were carried out to describe the behavior in solution of heterodimer, single epitopes, and epitopes loaded into MHC-II complexes. In order to predict T and B cell epitopes for antigenic activation, bioinformatic tools were used. Hence, we propose three epitopes with the potential to design pulmonary tuberculosis vaccines. The possible use of the proposed epitopes includes subunit vaccines, as a booster in BCG vaccination to improve its immune response, as well as the generation of antibodies that interfere with the Mycobacterium tuberculosis homeostasis, affecting its survival.

Integrating tuberculosis and COVID-19 molecular testing in Lima, Peru: a cross-sectional, diagnostic accuracy study.

BACKGROUND: Integrated molecular testing could be an opportunity to detect and provide care for both tuberculosis and COVID-19. Many high tuberculosis burden countries, such as Peru, have existing GeneXpert systems for tuberculosis testing with GeneXpert Xpert MTB/RIF Ultra (Xpert Ultra), and a GeneXpert SARS-CoV-2 assay, GeneXpert Xpert Xpress SARS-CoV-2 (Xpert Xpress), is also available. We aimed to assess the feasibility of integrating tuberculosis and COVID-19 testing using one sputum specimen with Xpert Ultra and Xpert Xpress in Lima, Peru. METHODS: In this cross-sectional, diagnostic accuracy study, we recruited adults presenting with clinical symptoms or suggestive history of tuberculosis or COVID-19, or both. Participants were recruited from a total of 35 primary health facilities in Lima, Peru. Participants provided one nasopharyngeal swab and one sputum sample. For COVID-19, we tested nasopharyngeal swabs and sputum using Xpert Xpress; for tuberculosis, we tested sputum using culture and Xpert Ultra. We compared diagnostic accuracy of sputum testing using Xpert Xpress with nasopharyngeal swab testing using Xpert Xpress. Individuals with positive Xpert Xpress nasopharyngeal swab results were considered COVID-19 positive, and a positive culture indicated tuberculosis. To assess testing integration, the proportion of cases identified in sputum by Xpert Xpress was compared with Xpert Xpress on nasopharyngeal swabs, and sputum by Xpert Ultra was compared with culture. FINDINGS: Between Jan 11, 2021, and April 26, 2022, we recruited 600 participants (312 [52%] women and 288 [48%] men). In-study prevalence of tuberculosis was 13% (80 participants, 95% CI 11-16) and of SARS-CoV-2 was 35% (212 participants, 32-39). Among tuberculosis cases, 13 (2·2%, 1·2-3·7) participants were concurrently positive for SARS-CoV-2. Regarding the diagnostic yield of integrated testing, Xpert Ultra detected 96% (89-99) of culture-confirmed tuberculosis cases (n=77), and Xpert Xpress-sputum detected 67% (60-73) of COVID-19 cases (n=134). All five study staff reported that integrated molecular testing was easy and acceptable. INTERPRETATION: The diagnostic yield of Xpert Xpress on sputum was moderate, but integrated testing for tuberculosis and COVID-19 with GeneXpert was feasible. However, systematic testing for both diseases might not be the ideal approach for everyone presenting with presumptive tuberculosis or COVID-19, as concurrent positive cases were rare during the study period. Further research might help to identify when integrated testing is most worthwhile and its optimal implementation. FUNDING: Canadian Institutes of Health Research and International Development Research Centre. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

UMOYA: a prospective longitudinal cohort study to evaluate novel diagnostic tools and to assess long-term impact on lung health in South African children with presumptive pulmonary TB-a study protocol.

BACKGROUND: Despite a high paediatric tuberculosis (TB) burden globally, sensitive and specific diagnostic tools are lacking. In addition, no data exist on the impact of pulmonary TB on long-term child lung health in low- and middle-income countries. The prospective observational UMOYA study aims (1) to build a state-of-the-art clinical, radiological, and biological repository of well-characterised children with presumptive pulmonary TB as a platform for future studies to explore new emerging diagnostic tools and biomarkers for early diagnosis and treatment response; and (2) to investigate the short and long-term impact of pulmonary TB on lung health and quality of life in children. METHODS: We will recruit up to 600 children (0-13 years) with presumptive pulmonary TB and 100 healthy controls. Recruitment started in November 2017 and is expected to continue until May 2023. Sputum and non-sputum-based samples are collected at enrolment and during follow-up in TB cases and symptomatic controls. TB treatment is started by routine care services. Intensive follow-up for 6 months will allow for TB cases to retrospectively be classified according to international consensus clinical case definitions for TB. Long-term follow-up, including imaging, comprehensive assessment of lung function and quality of life questionnaires, are done yearly up to 4 years after recruitment. DISCUSSION: The UMOYA study will provide a unique platform to evaluate new emerging diagnostic tools and biomarkers for early diagnosis and treatment response and to investigate long-term outcomes of pulmonary TB and other respiratory events on lung health in children.

HIV matters when diagnosing TB in young children: an ancillary analysis in children enrolled in the INPUT stepped wedge cluster randomized study.

BACKGROUND: Children under age five years, particularly those living with HIV (CLHIV), are at risk for rapid progression of tuberculosis (TB). We aimed to describe TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV compared to children without HIV in Cameroon and Kenya. METHODS: This sub-analysis of a cluster-randomized trial evaluating the integration of pediatric TB services from May 2019 to March 2021 enrolled children age < 5 years with TB. We estimated the HIV infection rate with 95% confidence interval (CI). We compared TB clinical presentations, diagnostic pathways and treatment outcomes in CLHIV and children without HIV. Finally, we investigated whether HIV infection was associated with a shorter time to TB diagnosis (≤ 3 months from symptoms onset) after adjusting for covariates. Univariable and multivariable logistic regression analysis were performed with adjusted odds ratios (AORs) presented as measures of the association of covariates with HIV status and with shorter time to TB diagnosis. RESULTS: We enrolled 157 children with TB (mean age was 1.5 years) and 22/157 (14.0% [9.0-20.4%]) were co-infected with HIV. CLHIV were more likely to initially present with acute malnutrition (AOR 3.16 [1.14-8.71], p = 0.027). Most TB diagnoses (140/157, 89%) were made clinically with pulmonary TB being the most common presentation; however, there was weak evidence of more frequent bacteriologic confirmation of TB in CLHIV, 18% vs. 9% (p = 0.067), due to the contribution of lateral-flow urine lipoarabinomannan to the diagnosis. HIV positivity (AOR: 6.10 [1.32-28.17], p = 0.021) was independently associated with a shorter time to TB diagnosis as well as fatigue (AOR: 6.58 [2.28-18.96], p = 0.0005), and existence of a household contact diagnosed with TB (AOR: 5.60 [1.58-19.83], p = 0.0075), whereas older age (AOR: 0.35 [0.15-0.85], p = 0.020 for age 2-5 years), night sweats (AOR: 0.24 [0.10-0.60], p = 0.0022) and acute malnutrition (AOR: 0.36 [0.14-0.92], p = 0.034) were associated with a delayed diagnosis. The case fatality rate was 9% (2/22) in CLHIV and 4% (6/135) in children without HIV, p = 0.31. CONCLUSIONS: These results altogether advocate for better integration of TB services into all pediatric entry points with a special focus on nutrition services, and illustrate the importance of non-sputum-based TB diagnostics especially in CLHIV. TRIAL REGISTRATION: NCT03862261, first registration 05/03/2019.

Strongyloidiasis-related lung involvement: too much of a bad thing.

PURPOSE OF REVIEW: Strongyloidiasis is a soil-transmitted helminthiasis, a neglected tropical disease that affects 300-900 million individuals globally. Strongyloides stercoralis is associated with cutaneous, respiratory, and gastrointestinal clinical manifestations. Chronicity is due to an autoinfective cycle, and host immunosuppression can lead to severe and fatal disease. Lung involvement is significant in severe strongyloidiasis, and Strongyloides has a complex association with a number of lung diseases, which will be discussed in this review. RECENT FINDINGS: The treatment of chronic lung diseases such as asthma and chronic obstructive pulmonary disease with corticosteroids is an important risk factor for Strongyloides hyperinfection syndrome (SHS)/disseminated strongyloidiasis. The use of corticosteroids in the treatment of coronavirus disease 2019 (COVID-19) and potentially COVID-19-induced eosinopenia are risk factors for severe strongyloidiasis. Recent findings have demonstrated a significant immunomodulatory role of Strongyloides in both latent and active pulmonary tuberculosis associated to an impaired immune response and poor outcomes in active pulmonary tuberculosis. SUMMARY: Strongyloides lung involvement is a common finding in severe infection. Prompt recognition of Strongyloides infection as well as prevention of severe disease by screening or presumptive treatment are important goals in order to improve Strongyloides outcomes in at-risk population.

The safety and immunogenicity of inactivated COVID-19 vaccine in old pulmonary tuberculosis patients.

The immunogenicity and safety of vaccines against coronavirus disease 2019 (COVID-19) remain unknown in patients with a history of pulmonary tuberculosis (OPTB). Therefore, the safety and effectiveness of inactivated vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were assessed in patients with a history of PTB. The study cohort included 106 healthy controls and 93 adult patients with OPTB who received a two-dose vaccination. The study period was 21 to 105 days. Concentrations of antibodies (Abs) against receptor-binding domain (RBD) IgG and SARS-CoV-2 neutralizing Abs (NAbs) were measured, in addition to the frequencies of SARS-CoV-2-specific B and a portion T cells. The incidence of adverse events was similar between the OPTB patients and healthy controls. No severe adverse events occurred. Concentrations of Abs against RBD-IgG and CoV-2 neutralizing Abs in addition to the frequencies of RBD-specific memory B cells proportions were lower in OPTB patients than the healthy controls (all, p < 0.05), while the frequencies of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4+) cells were higher (p = 0.023). There was no obvious correlation between age and blood concentrations of Abs against RBD-IgG and CoV-2 neutralizing Abs, while immune responses were similar in the fibrosis and calcification groups. The period of time following full-course vaccination and lymphocyte counts were associated to anti-RBD-IgG responses. Inactivated COVID-19 vaccinations were well tolerated in OPTB patients, although immunogenicity was limited in this population. This study has been registered at ClinicalTrials.gov (NCT05043246).

Limited effect of reducing pulmonary tuberculosis incidence amid mandatory facial masking for COVID-19.

Although the incidence and mortality rates associated with tuberculosis (TB) have been decreasing in many countries, TB remains a major public health concern. Obligatory facial masking and reduced health-care capacity because of COVID-19 may substantially influence TB transmission and care. The Global Tuberculosis Report 2021 published by the World Health Organization indicated a TB rebound at the end of 2020, which coincided with the COVID-19 pandemic. We explored this rebound phenomenon in Taiwan by investigating whether TB incidence and mortality are affected by COVID-19 because of their common route of transmission. In addition, we investigated whether the incidence of TB varies across regions with different incidences of COVID-19. Data (2010-2021) regarding annual new cases of TB and multidrug-resistant TB were collected from the Taiwan Centers for Disease Control. TB incidence and mortality were assessed in Taiwan's seven administrative regions. Over the last decade, TB incidence decreased continually, even during 2020 and 2021, the years coinciding with the COVID-19 pandemic. Notably, TB incidence remained high in regions with low COVID-19 incidence. However, the overall decreasing trends of TB incidence and mortality remained unchanged during the pandemic. Facial masking and social distancing may prevent COVID-19 transmission but exhibit limited efficacy in reducing TB transmission. Thus, during health-related policymaking, policymakers must consider TB rebound, even in the post-COVID-19 era.

Risk of Herpes Zoster in Patients with Pulmonary Tuberculosis-A Population-Based Cohort Study.

BACKGROUND: Pulmonary tuberculosis (TB), a global health problem, is typically caused by the bacterium Mycobacterium tuberculosis. Herpes zoster (HZ) is caused by the reactivation of the varicella-zoster virus (VZV). The reactivation of VZV can be caused by stress. We investigated whether pulmonary TB increases the risk of HZ development. METHODS: This study used data that sampled a population of 2 million people in 2000 from the National Health Insurance Research Database. This cohort study observed Taiwanese patients aged 20-100 years with pulmonary TB from 2000 to 2017 (tracked to 2018). Pulmonary TB was defined as having two or more outpatient diagnoses or at least one admission record. To address potential bias caused by confounding factors, the control cohort and pulmonary TB cohort were matched 1:1 by age, gender, index year, and comorbidities. Patients with HZ before the index date were excluded. RESULTS: A total of 30,805 patients were in the pulmonary TB and control cohorts. The incidence rate of HZ in pulmonary TB and control cohorts were 12.00 and 9.66 per 1000 person-years, respectively. The risk of HZ in the pulmonary TB cohort (adjusted hazard ratios = 1.23; 95% confidence interval = 1.16-1.30) was significantly higher than that of in control cohort. Among patients without comorbidities, the patients with TB were 1.28-fold more likely to have HZ than those without TB. CONCLUSION: Patients with TB should be well treated to avoid the potential risk of HZ occurrence. Although we identified the association between pulmonary TB and HZ, further studies are needed to confirm the result.

Time to diagnosis and treatment of pulmonary tuberculosis in indigenous peoples: a systematic review.

BACKGROUND: Time to diagnosis and treatment is a major factor in determining the likelihood of tuberculosis (TB) transmission and is an important area of intervention to reduce the reservoir of TB infection and prevent disease and mortality. Although Indigenous peoples experience an elevated incidence of TB, prior systematic reviews have not focused on this group. We summarize and report findings related to time to diagnosis and treatment of pulmonary TB (PTB) among Indigenous peoples, globally. METHODS: A Systematic review was performed using Ovid and PubMed databases. Articles or abstracts estimating time to diagnosis, or treatment of PTB among Indigenous peoples were included with no restriction on sample size with publication dates restricted up to 2019. Studies that focused on outbreaks, solely extrapulmonary TB alone in non-Indigenous populations were excluded. Literature was assessed using the Hawker checklist. Registration Protocol (PROSPERO): CRD42018102463. RESULTS: Twenty-four studies were selected after initial assessment of 2021 records. These included Indigenous groups from five of six geographical regions outlined by the World Health Organization (all except the European Region). The range of time to treatment (24-240 days), and patient delay (20 days-2.5 years) were highly variable across studies and, in at least 60% of the studies, longer in Indigenous compared to non-Indigenous peoples. Risk factors associated with longer patient delays included poor awareness of TB, type of health provider first seen, and self-treatment. CONCLUSION: Time to diagnosis and treatment estimates for Indigenous peoples are generally within previously reported ranges from other systematic reviews focusing on the general population. However among literature examined in this systematic review that stratified by Indigenous and non-Indigenous peoples, patient delay and time to treatment were longer compared to non-Indigenous populations in over half of the studies. Studies included were sparse and highlight an overall gap in literature important to interrupting transmission and preventing new TB cases among Indigenous peoples. Although, risk factors unique to Indigenous populations were not identified, further investigation is needed as social determinants of health among studies conducted in medium and high incidence countries may be shared across both population groups. Trial registration N/a.

A tale of three in symbiosis: TB-COVID-19-Bordetella coinfection.

Coinfections/mixed infections are common in the respiratory tract. Many times existing organisms have similar risk factors and clinical features that make the diagnosis difficult. Coronavirus diagnosed in 2019 (COVID-19) and tuberculosis (TB) are two such diseases. Patients with TB have lower cellular immunity and impaired pulmonary function. In such environment, atypical organisms, can infect and make the outcome unfavorable. A 21-year-old malnourished (body mass index- 15 kg/m2) girl presented with fever and cough for 10 days. Sputum for Cartridge Based Nucleic Acid Amplification Test demonstrated Mycobacterium tuberculosis with no rifampin resistance. Fever persisted (100-101°F) and saturation was dropping even after 10 days of antitubercular treatment. A repeat reverse transcription-polymerase chain reaction was done and was positive. In view of persistent symptoms after 20 days, bronchoscopy was done, and cultures showed Bordetella bronchiseptica. Fever and symptoms resolved completely after initiation of the sensitive drug. Diagnostic delay in coinfections can lead to increased morbidity and mortality.