Background: Chest radiography (CXR) is the most common imaging modality used to diagnose pulmonary tuberculosis (PTB). Accurate computer-aided detection (CAD) CXR software may aid physicians in low-resource, high tuberculosis (TB) endemic settings where radiologists are scarce. Methods: A retrospective pilot study comparing the assessment of humans and CAD was conducted on analogue CXRs from Guinea-Bissau and Ethiopia with the objective of comparing the interpretation of CXRs regarding PTB by CAD (qXR, Qure.ai) with that of two experienced Ethiopian radiologists (A and B). To improve the applicability of this method in low-resource settings, an analysis was performed on images of CXRs taken by mobile phones. Two reference standards were applied: final TB diagnosis by clinical or laboratory findings (i.e., GeneXpert (GX)-confirmed TB). Results: We included 498 CXRs. Radiologist A identified 50, radiologist B identified 99, and the software identified 81 as indicative of TB. The overall area under the curve (AUC) for the receiver operating characteristic (ROC) curve of the software was 0.84 for GX-confirmed cases. At the prechosen cut-off value of 0.5, the sensitivity of CAD CXR was 76.5%, and the specificity was 85.9%. Radiologist A’s assessments were 64.7% sensitive and 91.9% specific, while radiologist B´s assessments were 76.5% sensitive and 82.3% specific for GX-confirmed cases. The agreement regarding TB-related findings between the radiologists combined (k=0.45) and each radiologist and the software (k=0.56) was moderate. Conclusion: Our study revealed that CAD CXR performs comparably to experienced radiologists in diagnosing TB even when it is applied to analogue CXRs photographed by mobile phones. Trial registration: PACTR201611001838365

Objective: The aim of the study was to explore the association between tuberculosis (TB) and common mental disorders (CMD), in an area with high prevalence of TB.Methods: We performed a case-control study of TB patients and unmatched healthy controls, from a demographic surveillance site in Guinea-Bissau. Screening for CMD was performed once for controls and at inclusion and follow-up for TB patients. Kessler 10 (K-10) and a brief version of Hopkins Symptom Checklist 25 (SCL-8d) were used as screening instruments.Results: 571 controls were interviewed and 416 interviews were performed for 215 TB cases. Estimated CMD prevalence at the time of diagnosis of TB was 33.6 % (SCL-8d) and 46.2 % (K-10), compared with 6.8 % (SCL-8d) and 6.7 % (K-10) among controls; adjusted OR 7.18 (95 % CI 4.07 to 12.67) and 14.52 (95 % CI 8.15 to 25.84), respectively. No significant difference in CMD prevalence rates was observed between TB patients, after 6 months of treatment, and controls.Conclusion: Psychological distress and common mental disorders were more prevalent among TB patients at the time of diagnosis compared with the background population, but after completion of TB treatment no increased prevalence of psychological distress was found.

The number of patients with drug-resistant tuberculosis (DR-TB) is increasing worldwide. This review summarises the global epidemiology of DR-TB and current treatment challenges. Luckily, novel regimens comprising bedaquiline, pretomanid, linezolid, and moxifloxacin have seemingly mitigated the global threat posed by DR-TB. However, emerging resistance against bedaquiline and pretomanid, among other factors, persists as ongoing concerns in the global fight against DR-TB. While the new regimens are groundbreaking, the sustained development of novel drugs targeting the most resistant forms of tuberculosis is of utmost importance for future efforts against DR-TB.

We present the case of a patient with HIV and tuberculosis (TB) coinfection who initially developed paradoxical TB immune reconstitution inflammatory syndrome (TB-IRIS) post-antituberculous treatment and post-antiretroviral therapy initiation. Despite being managed effectively, lymphadenitis recurred as many as three times over the course of several years. Due to consistent culture-negative lymph node biopsies, the recurring lymphadenitis was eventually deemed inflammatory rather than microbiological recurrences. Cessation of anti-TB treatment led to symptom remission followed by a long asymptomatic period, corroborating the immunological nature of the episodes. However, 5 and 6 years after cessation of anti-TB treatment, respectively, lymphadenitis returned. In both instances, her symptoms regressed without treatment with anti-TB drugs. This case underscores the complexities of managing TB-IRIS and the necessity of differentiating between paradoxical TB-IRIS and other paradoxical reactions for appropriate treatment decisions. Recognition of such distinctions is crucial in guiding effective therapeutic interventions in TB-HIV coinfection scenarios.

A previously healthy man developed pulmonary symptoms 2 weeks after starting treatment with a tumour necrosis factor (TNF) inhibitor. A negative interferon-gamma release assay (IGRA) test was obtained prior to TNF inhibitor exposure, without consideration of the fact that the patient was already immunosuppressed and had a previous positive IGRA test 17 months earlier. The patient was treated for pneumonia twice but did not achieve remission. His physical health progressively deteriorated over the following months. Malignancy was suspected but not found. Eight months after the onset of symptoms,Mycobacterium tuberculosiswas found in samples from mediastinal lymph nodes, and the patient was diagnosed with multidrug-resistant tuberculosis (MDR-TB).This case illustrates the diagnostic challenge of TB, the need to raise awareness of the increased risk of TB in patients treated with TNF inhibitors and the need to increase knowledge regarding the effect of immunosuppressive agents on IGRA tests.

Delayed detection in TB due to structural and diagnostic shortcomings is pivotal for disease transmission, morbidity and mortality. We investigated whether an inclusive screening, followed by a structured clinical follow-up (FU) could improve case-finding.Patients were recruited from health centres in Bissau, Guinea-Bissau, and Gondar, Ethiopia. A routine FU was done at Week 2. If persisting symptoms were found, patients were investigated using chest X-ray (CXR) and Xpert® MTB/RIF, followed by a medical consultation. The main outcome were additional TB patients diagnosed by applying the FU strategy.Of 3,571 adults, 3,285 (95%) were examined at Week 2 FU, where 2,491 (72%) were asymptomatic. Screening patients presenting with cough >2 weeks alone contributed to the diagnosis of 93 patients (45% of all patients diagnosed here), whereas a TBscore >3 increased this by 18 (9%); adding a Week 2 FU yielded an additional 94 (46%) patients. Among the 794 (24%) with persisting symptoms, 25 were diagnosed using Xpert and 69 at clinical FU, which constituted 46% (94/205) of the total TB patients diagnosed.A Week 2 FU visit, which can be nested into routine healthcare, increased the diagnosis of TB patients by two-fold and avoids diagnostic gaps in the cascade-of-care..

Infections caused by Ureaplasma urealyticum in immune-competent people are typically simple and uncomplicated. However, in cases of immunosuppression, severe disseminated infections can occur.This case report describes the case of a severe, disseminated infection caused by U. urealyticum in a young female with unacknowledged humoral immunosuppression due to treatment with ocrelizumab for multiple sclerosis.The patient was admitted due to a recurrent episode of a tubo-ovarian abscess. Throughout the following 2 months of hospitalisation, treatment with several types of antibiotics and the placement of various drains led to no improvement. As extensive investigations indicated hypogammaglobulinaemia, U. urealyticum was suspected, and tests came back positive. Treatment with doxycycline and moxifloxacin led to a full recovery.This demonstrates how humoral immunosuppression is a risk factor for severe disseminated infections and how these may be avoided through monitoring of immunoglobulin levels in patients treated with ocrelizumab.

BACKGROUND:Growing evidence supports the existence of a sex difference in immunity to tuberculosis (TB). This is most often to the detriment of males. This study aimed to assess the association between scar size from bacillus Calmette-Guérin (BCG) and mortality risk stratified by sex.METHODS:Kaplan-Meier survivor functions and Cox proportional hazard models were used to assess mortality risk by sex and scar size. Groups were further compared by clinical and epidemiological characteristics.RESULTS:Between 2003 and 2019, 2944 eligible patients were identified, of whom 1003 were included in the final analysis. Males with BCG scars, particularly large scars, were less likely to die within 1 y of diagnosis than males with no scar (adjusted hazard ratio 0.36 [95% confidence interval 0.15 to 0.88]). In contrast, females with small scars trended towards higher mortality than females with no scars or females with large scars.CONCLUSIONS:BCG protects against death in male but not female patients with TB. More research is needed to determine the mechanisms underpinning these sex differences and whether they are generalizable beyond this setting.

Infections caused byUreaplasma urealyticumin immune-competent people are typically simple and uncomplicated. However, in cases of immunosuppression, severe disseminated infections can occur.This case report describes the case of a severe, disseminated infection caused byU. urealyticumin a young female with unacknowledged humoral immunosuppression due to treatment with ocrelizumab for multiple sclerosis.The patient was admitted due to a recurrent episode of a tubo-ovarian abscess. Throughout the following 2 months of hospitalisation, treatment with several types of antibiotics and the placement of various drains led to no improvement. As extensive investigations indicated hypogammaglobulinaemia,U. urealyticumwas suspected, and tests came back positive. Treatment with doxycycline and moxifloxacin led to a full recovery.This demonstrates how humoral immunosuppression is a risk factor for severe disseminated infections and how these may be avoided through monitoring of immunoglobulin levels in patients treated with ocrelizumab.

BACKGROUND:Few studies have assessed life expectancy of patients with tuberculosis (TB) against a comparable background population, particularly in low-income, high-incidence settings. This study aimed to estimate the life expectancy (LE) of patients with TB in the West African country of Guinea-Bissau and compare it with the LE of the background population.METHODS:This study used data from the Bandim TB cohort from 2004-20 as well as census data from the capital of Guinea-Bissau. LE was estimated using a bootstrapped Kaplan-Meier survival analysis for patients with TB and the background population, stratifying by age of entry and various patient subgroups. The analysis was further stratified by diagnosis period and length of schooling (an indicator of socioeconomic status), to assess their influence on LE. A sensitivity analysis was performed assuming death at loss to follow-up.RESULTS:The analysis included 2278 patients and a background population of 169 760 individuals. Overall median LE among 30-year-old patients with TB was 10.7 years (95% CI: 8.7-12.6), compared with 35.8 (95% CI: 35.1-36.5) in the background population. LE was shorter in HIV-infected patients and those who had unsuccessful treatment outcome; however, even among those who were both uninfected with HIV and experienced successful treatment outcome, LE was 20% shorter than in the background population. Longer schooling appeared to decrease mortality.CONCLUSIONS:TB substantially shortens LE. This effect is present even in patients who are uninfected with HIV and who have successful treatment outcome.

OBJECTIVES:Previous studies have found declining incidence of tuberculosis (TB) in Bissau, Guinea-Bissau. This study aimed to report incidence rates of TB for the period 2004-2020, stratifying by sex, smear-status, and HIV-status, as well as describe developments in TB case fatality rate and diagnostic delay.DESIGN AND METHODS:Data from the Bandim Health Project HDSS and the TB registry from Jan 1st, 2004 to Dec 31st, 2020 were used. Incidence rates were calculated for each year and for smear-positive, smear-negative, HIV-positive, HIV-negative, and unknown HIV-status. Incidence rate ratio and test for trend were done using a one-step Newton approximation to the log-linear Poisson regression coefficient.RESULTS:Overall TB incidence declined only slightly over the period from 294 per 100,000 in 2004 to 273 in 2020. TB/HIV coinfection declined from 108 in 2004 to 14 in 2020, as did incidence among females and smear-negative cases.CONCLUSIONS:Incidence of PTB in Bissau, Guinea-Bissau is declining slowly, if at all. TB incidence among females, smear-negative TB, TB case fatality rate, and TB/HIV coinfection and diagnostic delay are declining.

SETTING: In an urban demographic, high TB burden surveillance site in Guinea-Bissau, most deaths occur at home, and information on cause of death (CoD) is lacking.OBJECTIVE: To examine CoD and the proportion of TB deaths in three groups: among patients examined for TB without a verified diagnosis after diagnostic workup, described as “assumed TB-negative” (aTBneg), among patients with a confirmed diagnosis of TB and in a sample of the background population.DESIGN: Verbal autopsies (VAs) were obtained for registered deaths occurring between 1 January 2010 and 15 June 2016. All deaths among aTBneg and patients with TB, and a sample of deaths in the background population were included.RESULTS: VAs were obtained from 104/112 aTBneg patients, 140/155 patients with TB, and 172/219 from the general population. The leading CoD was TB in respectively 20%, 69% and 9% of the cohorts. HIV/AIDS-related deaths were the most frequent CoD among aTBneg patients (45%) and in the background population (27%), and accounted for 9% of patients with TB.CONCLUSION: TB was shown to be a frequent CoD, not only among patients diagnosed with TB, but also among aTBneg patients and the background population. This indicates a low TB case detection rate.

BACKGROUND: Health-related quality of life (HRQoL) in patients with pulmonary TB may be predictive of disease outcome; however, HRQoL instruments are often complicated and unsuitable for use in low-resource settings. A single-item self-rated health (SRH) score may represent a simpler alternative which could be used in clinical decision-making.AIMS: To evaluate internal and external validity of SRH and its correlation with TBscore/TBscoreII in a low-resource setting.METHODS: We used data from our ongoing prospective TB cohort study in Guinea-Bissau. Cohen´s d was used to assess internal validity, and receiver-operating characteristics and mortality statistics to assess external validity. Correlation between SRH and TBscore/TBscoreII was estimated using linear regression.RESULTS: SRH showed satisfactory internal validity and ability to discriminate between fatal cases at high and low scores, although not at middling scores. SRH and TBscore/TBscoreII correlated well at each examination but changes in scores did not, which may be due to ceiling/floor effects and a lag between disease severity and HRQoL.CONCLUSION: SRH shows potential as a quick and simple method to identify patients in need of intensified follow-up during treatment provision. More research is needed to assess its generalisability beyond our setting and to develop models for clinical use of SRH.

Objective: Both tuberculosis (TB) and tobacco smoking are preventable health hazards. Few studies have examined the relationship between TB and tobacco smoking in an African setting, where the two health burdens collide heavily. This study aimed to describe the severity of TB disease and treatment outcomes among smokers with TB compared with nonsmokers with TB in Guinea-Bissau. Methods: We conducted a prospective follow-up study between 2003-2017 in Guinea-Bissau, enrolling adult patients with TB classified as nonsmokers or smokers. Disease severity was assessed using the Bandim TBscore. Multivariate logistic and Cox proportional hazard regressions were used to analyse treatment outcomes. Results: Of 1780 included patients, 385 were smokers who had smoked for a median 10 years (interquartile range [IQR] 5-20). No difference in disease severity at the time of diagnosis was observed. Smokers were not significantly more prone to a nonsuccessful treatment outcome, although a trend was seen (adjusted odds ratio [OR] 1.24, 95% confidence interval [CI] 0.91-1.70), and smokers tended to be more often lost to follow-up, but this also was not a significant finding (adjusted hazard ratio [HR] 2.09, 95% CI 0.89-4.94). Conclusion: In a TB high-endemic setting with few tobacco smokers, smoking was not associated with disease severity or worse outcome, possibly because of socioeconomic confounders.

BACKGROUNDGlobally, more males than females are diagnosed with pulmonary TB (PTB); however, the cause of this gender disparity remains unknown. We aimed to assess gender differences in an observational cohort of patients with presumed PTB (prePTB) at the Bandim Health Project, Guinea-Bissau.METHODSAdult patients with signs and symptoms suggestive of PTB seeking medical care were invited to participate and were referred to comprehensive diagnostic work-up.RESULTSWe included 2020 patients with prePTB; 54.6% were female. Females were younger than males and more often infected with HIV. More male patients with prePTB were diagnosed with PTB and the proportion of smear-positive cases was greater among males. There was no gender difference in loss to follow-up during the diagnostic process. Of 219 patients with PTB, 205 started treatment, with no difference between genders regarding pretreatment loss to follow-up or treatment outcome.CONCLUSIONSMore women sought help for symptoms indicative of PTB, yet more men were diagnosed. Women did not have more clinically severe disease at presentation, did not drop out of diagnostic procedures more frequently and did not experience a worse outcome than men. This suggests that the gender gap in PTB is unlikely to be due solely to differences in care-seeking behaviour or diagnostic procedures in our setting.

Background The World Health Organization (WHO) recommends active case-finding (ACF) of tuberculosis (TB) in certain high-risk groups; however, more evidence is needed to elucidate the scope of ACF beyond the current recommendations. In this study we aimed to systematically review yields (the prevalence of active TB) of studies on ACF in general populations and at-risk groups. Methods A literature search in PubMed, Embase and the Cochrane Central Library (CENTRAL) was performed for studies concluded after 31 December 1999 and published before 1 September 2020. Screening yields were estimated and yield/prevalence ratios (ratio between yield of study and WHO estimated prevalence of TB) were calculated to assess which groups might especially benefit from ACF. Finally, risk of bias was assessed and heterogeneity was investigated using meta-regression and sensitivity analyses. Results We included 197 studies, with a total of 12 372 530 screened and 53158 cases found. Yields were high among drug users, close contacts, the poor and marginalised, people living with HIV, and prison inmates across incidence strata, and estimated yield/prevalence ratios in screenings of general populations tended to be >1 with an overall ratio of 1.4 and ranging between 1.0 and 1.5. Sensitivity analyses suggested that inclusion of studies at high risk of bias contributed to underestimation of yields. Conclusion Despite many studies using insensitive screening methods, these results suggest that more at risk groups should be considered for inclusion in future screening recommendations and that screening of general populations may outperform current case-finding practices, providing evidence for extending ACF beyond the current recommendations.

On March 24th 1882 Koch's announcement in Berlin of the discovery of the microbial cause of tuberculosis (TB), Mycobacterium tuberculosis, heralded a major breakthrough, bringing hope for a devastating disease which at that time caused the death of one in seven people in Europe and the Americas. (Wallstedt and Maeurer, 2015Wallstedt H. Maeurer M. The history of tuberculosis management in Sweden.Int J Infect Dis. 2015; 32: 179-182Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar). One hundred and twenty years later, and despite the availability of effective treatment for the past 6 decades, 1.4 million people die of TB annually (WHO, 2021aWHO Global tuberculosis report 2020. World Health Organization, 2021https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdfGoogle Scholar). Over the past 15 months, the unprecedented COVID-19 pandemic has disrupted health services globally (Cilloni et al., 2020Cilloni L. Fu H. Vesga J.F. Dowdy D. Pretorius C. Ahmedov S. et al.The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis.EClinicalMedicine. 2020; 28100603https://doi.org/10.1016/j.eclinm.2020.100603Abstract Full Text Full Text PDF PubMed Scopus (146) Google Scholar) and has negatively impacted on gains being made in global TB control efforts to achieve End TB targets (Sahu et al., 2020Sahu S. Ditiu L. Lawson L. Ntoumi F. Arakaki D. Zumla A. UN General Assembly tuberculosis targets: are we on track?.Lancet. 2020; 395: 928-930Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar; STOP TB, 2019). The theme of this year's World TB Day March 24th, 2021, 'The Clock is Ticking' (WHO, 2021bWHO World Tuberculosis Day 2021 The Clock is Ticking.2021https://www.who.int/campaigns/world-tb-day/world-tb-day-2021Google Scholar), conveys the sense of urgency that the world is running out of time to deliver the commitments to End TB made by global leaders at the United Nations General Assembly high level meeting on TB (UNGA, 2018UNGA United Nations General Assembly resolution A/RES/73/3; October 2018. Political declaration of the high-level meeting of the General Assembly on the fight against tuberculosis.2018https://www.un.org/en/ga/search/view_doc.asp?symbol=A/RES/73/3Google Scholar). This theme is particularly appropriate and critical in light of the devastating COVID-19 pandemic which is currently the top killer from an infectious disease globally, with TB now being shifted to second place (WHO, 2021aWHO Global tuberculosis report 2020. World Health Organization, 2021https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdfGoogle Scholar, WHO, 2021cWHO COVID-19 dashboard.2021https://covid19.who.int/Google Scholar). Since the end of December, 2019, when the WHO was made aware of several cases of atypical pneumonia in Wuhan, China, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as of March 15th 2021, there have been 119,603,761 confirmed COVID-19 cases, with 2,649,722 deaths, reported to WHO (WHO, 2021cWHO COVID-19 dashboard.2021https://covid19.who.int/Google Scholar). In commemoration of World TB Day March 24th, 2021, the International Journal of Infectious Diseases is once again publishing a specific TB Theme issue of 18 articles covering a range of topics. The October 2020 WHO Global TB report and the United Nations (UN) Secretary-General's 2020 progress report on TB, are reviewed by Chakaya et al., 2021Chakaya J. Khan M. Ntoumi F. Aklillu E. Fatima R. Mwaba P. et al.Global Tuberculosis Report 2020 — Reflections on the Global TB burden, treatment and prevention efforts.Int J Infect Dis. 2021; 113: S7-S12Abstract Full Text Full Text PDF Scopus (393) Google Scholar. They reflect on current TB control strategies in light of the United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York (UNGA, 2018UNGA United Nations General Assembly resolution A/RES/73/3; October 2018. Political declaration of the high-level meeting of the General Assembly on the fight against tuberculosis.2018https://www.un.org/en/ga/search/view_doc.asp?symbol=A/RES/73/3Google Scholar). Progress in achieving TB control targets has been very slow. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208,000 deaths among people living with HIV. In addition, preliminary assessments of how the unprecedented, devastating COVID-19 pandemic is affecting TB health services, interrupting and slowing down treatment and prevention efforts. It is anticipated that the End TB strategy target of ending TB by 2035 will not be met. The WHO 2020 TB Report (WHO, 2021aWHO Global tuberculosis report 2020. World Health Organization, 2021https://apps.who.int/iris/bitstream/handle/10665/336069/9789240013131-eng.pdfGoogle Scholar) states that a 50% drop in the number of people with TB detected, could result in up to 400,000 additional TB deaths in a year. Innovative plans are needed to maintain all TB services as well as access to these services, in the wake of the COVID-19 pandemic and investments in the development of low-cost rapid diagnostic tests for both COVID-19 and TB are urgently needed. There needs to be a rejuvenated, sustained, and concerted effort to identify and treat 'missing people with TB'. Governments of high TB incidence countries need to ensure there are rapid TB diagnostic services available in every health facility, so all TB cases can be reached. Global health inequities that underlie differences in TB disease burden, as well as daunting environmental health challenges, need to be addressed by multiple approaches and sectors. Fox et al., 2021Fox G.J. Nguyen T.A. Coleman M. Trajman A. Velen K. Marais B.J. Mycobacterium tuberculosis; latent tuberculosis; preventive therapy; prophylaxis; patient-centered care.Int J Infect Dis. 2021; 113: S13-S15Abstract Full Text Full Text PDF Scopus (4) Google Scholar highlight that latent tuberculosis infection affects one quarter of the world's population and that despite effective oral treatment regimens being available, scale-up and rollout of TB preventive treatment (TPT) remains limited. They describe strategies to support scale-up of TPT in high-prevalence settings, where the potential benefit for affected individuals is considerable and emphasise that patients must be at the centre of TPT policies. Addressing health system requirements for scale-up will be important to ensure that programs can deliver treatment safely, efficiently and sustainably. Nachega et al., 2021aNachega J.B. Kapata N. Sam-Agudu N.A. Decloedt E.H. Katoto P.D.M.C. Nagu T. et al.Minimizing the impact of the triple burden of COVID-19, tuberculosis and HIV on health services in sub-Saharan Africa.Int J Infect Dis. 2021; 113: S16-S21Abstract Full Text Full Text PDF Scopus (27) Google Scholar discuss the negative impact of COVID-19 on TB and HIV health services. They suggest approaches to mitigate the growing burden of these colliding epidemics in sub-Saharan Africa, which bear the highest proportions of TB and HIV cases worldwide. The COVID-19 pandemic has added an additional burden to already overstretched health systems, which, among many other things, were struggling to deal with the longstanding dual epidemics of TB and HIV. Knipper et al., 2021Knipper M. Sedas A.C. Keshavjee S. Abbara A. Almhawish N. Alashawi H. et al.The need for protecting and enhancing TB health policies and services for forcibly displaced and migrant populations during the ongoing COVID-19 pandemic.Int J Infect Dis. 2021; 113: S22-S27Abstract Full Text Full Text PDF Scopus (7) Google Scholar review the COVID-19 pandemic threat to derailing health services for forcibly displaced people and migrant populations, populations who face specific vulnerabilities placing them at increased risk of developing TB if they have LTBI, or not being diagnosed as having active TB. Highlighting three case studies as examples—from Peru, South Africa, and Syria—they illustrate the lived experience of forced migration and mobile populations, and the impact of COVID-19 on TB among these populations. They indicate that addressing TB, COVID-19 and migration from a syndemic perspective, not only draws systematic attention to comorbidity and the relevance of social and structural context, but also helps to find solutions. The true reality of syndemic interactions can only be fully understood by considering a particular population and bio-social context and ensuring that they receive the comprehensive care that they need. It also provides avenues for strengthening and expanding the existing infrastructure for TB care to tackle both COVID-19 and TB in migrants and refugees in an integrated and synergistic manner. Over a quarter of the individuals diagnosed with TB in the European Union region are born outside the EU and the proportion has been increasing steadily. Over 50% of TB cases in Italy are foreign born migrants. Goscé et al., 2021Goscé L. Girardi E. Allel K. Cirillo D.M. Barcellini L. Stancanelli G. et al.Tackling TB in migrants arriving at Europe's southern border.Int J Infect Dis. 2021; 113: S28-S32Abstract Full Text Full Text PDF Scopus (1) Google Scholar describe the EDETECT-TB project in Italy which implemented and evaluated active TB screening in the migrant population and their study confirmed that early case detection is a cost-effective intervention and that targeted post-arrival early screening ensures that potential further transmission is averted. Recurrent pulmonary TB is a growing, important and neglected problem affecting treated TB patients and TB health services across the world, particularly in sub-Saharan Africa and Asia. Analyses and identification of differences in clinical features between recurrent PTB and newly diagnosed PTB may lead to improved management recommendations. Nagu et al., 2021Nagu T.J. Mboka M.A. Nkrumbih Z.F. Shayo G. Mizinduko M.M. Komba E.V. et al.Clinical and imaging features of adults with recurrent pulmonary tuberculosis — a prospective case-controlled study.Int J Infect Dis. 2021; 113: S33-S39Abstract Full Text Full Text PDF Scopus (4) Google Scholar performed a prospective case-controlled study of clinical and imaging features of patients with recurrent pulmonary TB (RPTB) and compared them with those of newly diagnosed PTB cases. They found that hemoptysis, lung parenchymal damage, and patients being older than 45 years of age are significant features of RPTB, suggesting that management of TB cases should focus on risk factors for recurrence, and design a more holistic model of care to prevent long term lung injury. Kizny Gordon et al., 2021Kizny Gordon A. Marais B. Walker T.M. Sintchenko V. Clinical and public health utility of Mycobacterium tuberculosis whole genome sequencing.Int J Infect Dis. 2021; 113: S40-S42Abstract Full Text Full Text PDF Scopus (15) Google Scholar review the clinical and public health utility benefits of M. tuberculosis whole genome sequencing (WGS), including provision of more rapid and complete information on drug-resistance, detection of transmission clusters, contamination events, mixed infections, and to differentiate between re-infection and relapse. They also discuss future advances that have the potential to change the landscape of TB diagnostics and management, such as culture-free sequencing and surveillance of antimicrobial resistance to guide precision medicine approaches, as well as some of the challenges involved. Whole genome sequencing-based differentiation between re-infection and relapse in TB cases has important implications for public health, especially in patients with human immunodeficiency virus (HIV) co-infection. Shanmugam et al., 2021Shanmugam S. Bachmann N.L. Martinez E. Menon R. Narendran G. Narendran S. et al.Whole genome sequencing based differentiation between re-infection and relapse in Indian patients with tuberculosis recurrence, with and without HIV co-infection.Int J Infect Dis. 2021; 113: S43-S47Abstract Full Text Full Text PDF Scopus (8) Google Scholar compared Mycobacterial Interspersed Repeat Unit (MIRU) typing and spoligotyping with WGS to differentiate between relapse and re-infection and assessed the value of WGS to track acquired drug resistance in those with relapse after successful treatment. Comparing M. tuberculosis genomes, they found that 95% of TB recurrences in the HIV-negative cohort were due to relapse, while the majority of TB recurrences in the HIV-positive cohort were due to re-infection, highlighting the need for effective infection control in HIV care setting. WGS for M. tuberculosis drug resistance detection is now available in diagnostic and reference laboratories worldwide. Characterizing novel mutations and deletions associated with drug resistant M. tuberculosis could ultimately lead to better treatment outcomes. The additional value WGS provides in inferring drug resistance is discussed by Lam et al., 2021Lam C. Martinez E. Crighton T. Furlong C. Donnan E. Marais B.J. et al.Value of routine whole genome sequencing for Mycobacterium tuberculosis drug resistance detection.Int J Infect Dis. 2021; 113: S48-S54Abstract Full Text Full Text PDF Scopus (18) Google Scholar. They sequenced genomes from all M. tuberculosis isolates in NSW, Australia, collected between 2016 and 2019 and tracked the prevalence of drug resistance and circulation of predominant M. tuberculosis lineages. They demonstrated that WGS was able to capture an additional 20% of drug resistance mutations not detected by commercial diagnostic assays, signaling the additional value that WGS offers over existing genotypic drug resistance assays in terms of sensitivity. The Bandim TBscore is a clinical score that predicts treatment outcome in TB patients and may prove useful as an indicator of which healthcare-seeking adults to refer for sputum smear microcopy. Rudolf et al., 2021Rudolf F. Abate E. Moges B. Mendes A.M. Mengistu M.Y. Sifna A. et al.Increasing smear positive tuberculosis detection using a clinical score — A stepped wedge multicenter trial from Africa.Int J Infect Dis. 2021; 113: S55-S62Abstract Full Text Full Text PDF Scopus (3) Google Scholar conducted a stepped wedge cluster-randomized trial at six health centers in Bissau, Guinea-Bissau, and Gondar, Ethiopia. They conclude that it is an implementable approach and solution to an old and yet unresolved challenge. Using the TBscore for triage before smear microscopy may improve case detection and decrease mortality if there is sufficient laboratory capacity to increase sputum smears. Marais et al., 2021Marais B.J. Verkuijl S. Casenghi M. Triasih R. Hesseling A.C. Mandalakas A.M. et al.Paediatric tuberculosis — new advances to close persistent gaps.Int J Infect Dis. 2021; 113: S63-S67Abstract Full Text Full Text PDF Scopus (9) Google Scholar discuss new advances to close persistent gaps in the prevention and diagnosis of childhood TB. Almost all children estimated in the Global TB Report 2020 to have died from TB were never diagnosed or offered TB treatment. Thus new approaches are required to ensure that effective TB prevention strategies are implemented and to improve the accuracy of current and new diagnostic (rule-in and rule-out) tests. Reducing the major gaps in TB preventive treatment (TPT) will require strong political commitment and concerted effort, with major upscaling of household contact investigation. While widespread roll-out of Xpert MTB/RIF Ultra® should be supported and could improve case detection in young children, they caution that specimen collection remains difficult and test sensitivity low. The use of non-sputum specimens are essential to improve diagnostic access, but given the limited accuracy of all available tests and the excellent tolerance of TB drugs in children the global community may have to accept some over-treatment using the most feasible approaches available; if we are serious about closing the persistent case detection gap in young children. Zoonotic TB is evolving in an everchanging global landscape. Despite slow reductions in the annual burden of active TB cases, Zoonotic TB (zTB) remains a poorly monitored and poorly addressed global burden. Kock et al., 2021Kock R. Michel A.L. Yeboah-Manu D. Azhar E.I. Torrelles J.B. SI et al.Zoonotic tuberculosis — the changing landscape.Int J Infect Dis. 2021; 113: S68-S72Abstract Full Text Full Text PDF Scopus (16) Google Scholar in their zoonotic TB review highlight the higher incidence in some specific regions and countries, especially where close association exists between growing numbers of cattle (the major source of Mycobacterium bovis (M. bovis) and people, many suffering from poverty and where milk or dairy products are consumed un-pasteurized. Attention needs to be re-focused to prevent a rapid increase in zTB disease along with growing intensification of dairy production. Evidence of new zoonotic mycobacterial strains such as M. orygis, especially in South Asia and Africa warrants rapid assessment of drivers and risk, and the development of appropriate interventions. Control of M. bovis in cattle through early detection of infection and disease, as well as pasteurization of dairy products, remains the mainstay of reducing zTB risk to humans, while new point of care diagnostics will help to detect and appropriately treat human cases. Lipman et al., 2021Lipman M. Kunst H. Loebinger M.R. Milburn H.J. King M. Non tuberculous mycobacteria pulmonary disease: patients and clinicians working together to improve the evidence base for care.Int J Infect Dis. 2021; 113: S73-S77Abstract Full Text Full Text PDF Scopus (6) Google Scholar highlight that pulmonary disease caused by non-tuberculous mycobacteria (NTM) is often missed, is difficult to treat successfully in an often frail population with other chronic conditions such as bronchiectasis and COPD, is on the rise globally, and results in significant morbidity and even mortality. They identify and discuss key issues in NTM management. In addition to the need for research into epidemiology, immunology and treatment, they recommend an 8-point plan including greater use of patient and clinician networks to educate primary and secondary care clinicians and promote a multidisciplinary team approach with shared patient-clinician decision making throughout care. They also call for co-ordinated patient-focused research to improve what is often a limited evidence base to guide management. Nachega et al., 2021bNachega J.B. Maeurer M. Sam-Agudu N.A. Chakaya J. Katoto P.D.M. Zumla A. Bacille Calmette-Guérin (BCG) vaccine and potential cross-protection against SARS-CoV-2 infection — Assumptions, knowns, unknowns and need for developing an accurate scientific evidence base.Int J Infect Dis. 2021; 113: S78-S81Abstract Full Text Full Text PDF Scopus (7) Google Scholar re-ignite the century old controversies on the Bacille Calmette–Guérin (BCG) vaccine, which is yet again a focus of global attention—this time due to the global COVID-19 pandemic caused by SARS-CoV-2) Their viewpoint focusses on the assumptions, knowns, unknowns and need for developing an accurate scientific evidence base for suggestions of potential cross-protection against SARS-CoV-2 infection. Recent studies have shown that human CD4+ and CD8+ T-cells primed with a BCG-derived peptide developed high reactivity to its corresponding SARS-CoV-2-derived peptide. Furthermore, BCG vaccine has been shown to substantially increase interferon-gamma (IFN-γ) production and its effects on CD4+ T-cells and these nonspecific immune responses could be harnessed as cross protection against severe forms of COVID-19. They highlight that there are numerous clinical trials in progress to determine the effectiveness of BCG vaccination for prevention of SARS-CoV-2 infection or to reduce morbidity and mortality associated with COVID-19. Data from ongoing BGG trials may shed light on the mechanisms underlying BCG-mediated immunity and could lead to improved efficacy, increased tolerance of treatment, and identification of benefits combining BCG and COVID-19 vaccines, or other adjunct immunotherapies. There are several ongoing studies which are defining the interactions between COVID-19 and TB. Petrone et al., 2021Petrone L. Petruccioli E. Vanini V. Cuzzi G. Gualano G. Vittozzi P. et al.Coinfection of tuberculosis and COVID-19 limits the ability to in vitro respond to SARS-CoV-2.Int J Infect Dis. 2021; 113: S82-S87Abstract Full Text Full Text PDF Scopus (54) Google Scholar evaluated IFN-γ levels in whole blood after stimulation with Mtb antigens in the Quantiferon-Plus format or with peptides derived from SARS-CoV-2 spike protein, Wuhan-Hu-1 isolate (CD4-S). They demonstrated for the first time that COVID-19 patients, either with TB or LTBI, have a low ability to build an immune response to SARS-CoV-2 while retaining the ability to respond to Mtb-specific antigens. These results may have important implications for the clinical management of COVID-19 individuals coinfected with Mtb. Fatima et al., 2021Fatima R. Akhtar N. Yaqoob A. Harries A.D. Khan M.S. Building better tuberculosis control systems in a post-COVID world: learning from Pakistan during the COVID-19 pandemic.Int J Infect Dis. 2021; 113: S88-S90Abstract Full Text Full Text PDF Scopus (12) Google Scholar focus on TB control in Pakistan and discuss the importance of a multi-pronged approach for building better TB control systems to cope with the effects of COVID-19. As in all high-TB endemic countries, COVID-19 is impacting negatively in Pakistan. The COVID-19 has provided an opportunity in country to introduce some adaptations to bring TB care closer to communities, increased investments in human resources and addressing stigma, and implementation of telemedicine systems for follow-up and consultations. Global health inequities driving TB epidemiology, including the environment and climate control, gender, age, socio-economic status, and wealth as well as resource distribution, need to be addressed by multiple approaches and sectors. The WHO 2020 global TB Report estimates that in 2019 there were an estimated 500,000 cases of multi-drug resistant TB (MDR-TB) of which only 186,772 MDR-TB cases were diagnosed, and positive treatment outcomes were achieved in 57% of them. These data highlight the need for accelerating and improving MDR-TB screening, diagnostic, treatment and patient follow-up services. Maretbayeva et al., 2021Maretbayeva S.M. Rakisheva A.S. Adenov M.M. Yeraliyeva L.T. Algozhin Y.Z. Stambekova A.T. et al.Culture conversion at six months in patients receiving bedaquiline- and delamanid-containing regimens for the treatment of multidrug-resistant tuberculosis in Kazakhstan.Int J Infect Dis. 2021; 113: S91-S95Abstract Full Text Full Text PDF Scopus (6) Google Scholar present the first study from Kazahstan on culture conversion at six months in patients receiving bedaquiline- and delamanid-containing regimens for the treatment of MDR-TB. Tiberi et al., 2021Tiberi S. Vjecha M.J. Zumla A. Galvin J. Migliori G.B. Zumla A. Accelerating development of new shorter TB treatment regimens in anticipation of a resurgence of multi-drug resistant TB due to the COVID-19 pandemic.Int J Infect Dis. 2021; 113: S96-S99Abstract Full Text Full Text PDF Scopus (25) Google Scholar emphasize that the direct and indirect negative impacts of COVID-19 on health services overall, including national TB programs and TB services add further to longstanding challenges for tackling MDR-TB such as availability of budgets, rollout of TB diagnostics and TB drugs. Implementation of latest WHO guidelines for MDR-TB, in light of COVID-19 disruption of TB services will be difficult and, it is anticipated the numbers of MDR-TB cases will rise in 2021 and 2022 and will affect MDR-TB treatment outcomes further. Investing more in development of new TB drugs and shorter MDR-TB treatment regimens is required in anticipation of emerging drug resistance to new TB drug regimens. These include closely aligning and optimizing COVID-19 and MDR-TB algorithms and improving clinical capacity to offer rapid diagnosis, quality treatment and follow up, and ensuring availability of quality, regular supply of cost-free TB drugs (for both DS-TB and MDR-TB) through improved procurement and distribution of TB drugs. Sahu et al., 2021Sahu S. Ditiu L. Sachdeva K.S. Zumla A. Recovering from the impact of the Covid-19 pandemic and accelerating to achieving the United Nations General Assembly tuberculosis targets.Int J Infect Dis. 2021; 113: S100-S103Abstract Full Text Full Text PDF Scopus (15) Google Scholar remind us that it has been over two years since global leaders signed the UN General Assembly high level meeting on TB (UNGA-HLM-TB) declaration which committed to mobilize 15 billion USD per annum for TB, 13 billion USD for TB care and 2 billion USD per annum for TB R&D (UNGA, 2018UNGA United Nations General Assembly resolution A/RES/73/3; October 2018. Political declaration of the high-level meeting of the General Assembly on the fight against tuberculosis.2018https://www.un.org/en/ga/search/view_doc.asp?symbol=A/RES/73/3Google Scholar). They point out that the follow up October 21, 2020 UN Secretary-General report (UNGA, 2020UNGA UN General Assembly 75th session September 2020. Progress towards the achievement of global tuberculosis targets and implementation of the political declaration of the high level meeting of the General Assembly on the fight against tuberculosis: Report of the Secretary-General.2020https://undocs.org/en/A/75/236Google Scholar) on progress towards implementation of the UNHLM political declaration on TB stresses that although high-level commitments and targets had galvanized global and national progress towards ending TB, urgent and more ambitious investments and actions were required, especially in lieu of the COVID-19 pandemic where associated public health measures and travel restrictions, have disrupted health services universally. The report sets out 10 priority recommendations to get the world on track to reach agreed targets by 2022. Importantly, all countries should signup to these ten priority recommendations and the Global Fund needs to increase its current commitment to mitigating the impact of COVID-19 on TB services (Global Fund to Fight AIDS, 2020Global Fund to Fight AIDS Tuberculosis and malaria.2020Google Scholar). Additional supplementary measures and resources are required to reduce the accumulating pool of undetected people with TB. These should include ramped-up active case-finding with intensive community engagement and contact tracing to sustain awareness of recognizing and responding to symptoms suggestive of TB, using digital technology and other diagnostic tools, and an uninterrupted supply of quality TB drugs and care for all people with TB (Stop TB Partnership, 2020Stop TB Partnership A deadly divide: TB commitments vs TB realities: a communities report on progress towards the UN political declaration on the fight against TB and a call to action to close the gaps in TB targets.2020http://www.stoptb.org/assets/documents/communities/The%20Deadly%20Divide_TB%20Commitments%20vs%20TB%20Realities%20FINAL%20HLM%20Report.pdfGoogle Scholar). On World TB Day 2021, every political and community leader, and funding agency must get the message that it is time to reduce global inequities as we work towards a TB free world. While there is a continued need to develop new prevention and treatment tools for TB, obtaining the resources required for implementation of current TB diagnostic and management tools could significantly advance TB control efforts. World leaders need to urgently address and reverse the socio-economic and health services impact of the COVID-19 pandemic. As COVID-19 vaccines and public health measures start to have an effect on slowing down the COVID-19 outbreak, every effort must be made by to ensure that health services and prevention programs for TB are not compromised. The commitment of western governments to the rapid development and rollout of COVID-19 vaccines is commendable, but it is important to ensure that no-one is 'left behind'. It's now time for them to invest with equal commitment to ending the TB epidemic. Reality showed us that it can be achieved, if there is serious political will which is translated into measurable, tangible actions resulting in impactful deliverables. This article is part of a supplement entitled Commemorating World Tuberculosis Day March 24th, 2021: "The Clock is Ticking" published with support from an unrestricted educational grant from QIAGEN Sciences Inc. All authors have a specific interest in Tuberculosis and have contributed to articles in this special IJID issue for World TB Day 2021. All authors declare no other conflicts of interest Professors Zumla, Kock and Abubakar, and Drs Kapata and Haider, are members of the European and Developing Countries Clinical Trials Partnership project Pan-African Network on Emerging and Re-Emerging Infections (PANDORA-ID-NET, Grant Agreement RIA2016E-1609, (https://www.pandora-id.net/). Sir Prof Zumla is in receipt of a UK-National Institutes of Health Research senior investigator award and is a 2020 Mahathir Science Award Laureate. Professor Nachega is supported by the NIH/Fogarty International Center (FIC) grant numbers 1R25TW011217-01 (African Association for Health Professions Education and Research); 1D43TW010937-01A1 (the University of Pittsburgh HIV-Comorbidities Research Training Program in South Africa—Pitt-HRTP-SA); and 1R21TW011706-01. Prof Maeurer is a member of the innate immunity advisory group of the BMGF.

Background: The Bandim TBscore is a clinical score that predicts treatment outcome in Tuberculosis (TB) patients and proved useful as an indicator of which healthcare-seeking adults to refer for sputum smear microcopy. We aimed to test in a randomized trial if the TBscore could be used to enhance the detection of smear positive (SP) TB. Methods: We carried out a stepped wedge cluster-randomized trial at six health centers in Bissau, Guinea-Bissau, and Gondar, Ethiopia. The primary outcome was diagnostic yield for SP TB. Secondary outcomes were successful treatment and effect on overall 12 months mortality. The study was registered at the Pan African Clinical Trials Registry (PACTR201611001838365). Results: We included 3571 adults. Overall, there was no effect of the intervention on SP PTB detected (OR 1.39 (95%CI 0.75 – 2.56). Analysis stratified by country, showed that the TBscore increased case detection in Gondar (OR 4.05 (95%CI 1.67 – 9.85)) but no effect was found in Bissau (OR 0.47 (95%CI 0.22 – 1.05)) where take-up was much lower. Overall mortality decreased during the intervention (HR 0.31 (95%CI 0.13-0.72)). Conclusion: Using the TBscore for triage before smear microscopy may improve case detection and decrease mortality if there is sufficient laboratory capacity to increase sputum smears.

ObjectivesTuberculosis (TB) is associated with a number of non-communicable co-morbidities, which can complicate treatment and impair outcome. The aim of this study was to assess the impact of hypertension on disease severity, treatment outcome and survival in a cohort of patients with TB.MethodsA retrospective cohort study was conducted in Guinea-Bissau. Patients newly diagnosed with TB between November 2003 and June 2016 were included. Hypertension was defined as blood pressure ≥140/90 mmHg. Disease severity was assessed using the Bandim TBscore. Survival was assessed at the end of treatment and 2 years after treatment initiation.ResultsIn total, 1544 patients were included in this study. Hypertension was present in 12.8% of patients at inclusion. Patients with hypertension had slightly less severe TB, but were less likely to have a successful treatment outcome and had 64% higher mortality at 2-year follow-up (adjusted hazard ratio 1.64, 95% confidence interval 1.15–2.34). Mortality rates were highest in hypertensive female patients and patients aged ≥ 45 years.ConclusionPatients with high blood pressure at the start of TB treatment had a higher mortality rate at 2-year follow-up. Mortality rates were highest in hypertensive females and patients aged ≥ 45 years.

Background: Clinical scores are promising case-finding tools for tuberculosis (TB) among HIV-infected patients. The Bandim TBscore has been shown to increase the diagnostic yield among patients with presumed TB in general, but has not previously been tested among newly diagnosed HIV patients at high risk of TB. Methods: HIV-infected patients were included in this cross-sectional study. A pre-post-intervention study design was used to assess the outcome of a change in practice, i.e. the application of a clinical score (TBscore) consisting of 13 signs and symptoms to assess the need for further TB diagnostics. Patients with a TBscore >= 2 were evaluated using smear microscopy and Xpert MTB/RIF. A TB diagnosis was made based on microbiology or clinical evaluation. The sensitivity and specificity of the TBscore were compared with those of World Health Organization symptoms. Results: The TB prevalence among newly enrolled HIV-infected patients during the study period was 13.4% (22/164). Using the TBscore and a diagnostic algorithm, it was possible to increase the proportion of patients started on TB treatment from 2.7% (10/367) the year before the study to 10.4% (17/164) during the study period. Five patients diagnosed with TB were not started on TB treatment as they were lost to follow-up or died. With a cut-off value of 2, the TBscore had a sensitivity, specificity, positive predictive value, and negative predictive value of 95.5% (21/22), 36.9% (41/111), 23.1% (22/118), and 97.6% (41/42), respectively. Conclusion: The TBscore is useful for standardized TB screening among HIV-infected individuals and may be a valuable tool to prioritize patients at high risk of TB. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.