Real-time evaluation (RTE) supports populations (e.g., persons experiencing homelessness (PEH) to engage in evaluation of health interventions who may otherwise be overlooked. The aim of this RTE was to explore the understanding of TB amongst PEH, identify barriers/facilitators to attending screening for PEH alongside suggestions for improving TB-screening events targeting PEH, who have high and complex health needs. This RTE composed of free-text structured one-to-one interviews performed immediately after screening at a single tuberculosis (TB) screening event. Handwritten forms were transcribed for thematic analysis, with codes ascribed to answers that were developed into core themes. All RTE participants (n=15) learned about the screening event on the day it was held. Key concerns amongst screening attendees included: stigma around drug use, not understanding the purpose of TB screening, lack of trusted individuals/services present, too many partner organizations involved, and language barriers. Facilitators to screening included a positive welcome to the event, a satisfactory explanation of screening tests, and sharing of results. A need for improved event promotion alongside communication of the purpose of TB screening amongst PEH was also identified. A lack of trust identified by some participants suggests the range of services present should be reconsidered for future screening events.

Genomic epidemiology is routinely used worldwide to interrogate infectious disease dynamics. Multiple computational tools exist that reconstruct transmission networks by coupling genomic data with epidemiological models. Resulting inferences can improve our understanding of pathogen transmission dynamics, and yet the performance of these tools has not been evaluated for tuberculosis (TB), a disease process with complex epidemiology including variable latency and within-host heterogeneity. Here, we performed a systematic comparison of six publicly available transmission reconstruction models, evaluating their accuracy when predicting transmission events in simulated and real-world Mycobacterium tuberculosis outbreaks. We observed variability in the number of transmission links that were predicted with high probability (P ≥ 0.5) and low accuracy of these predictions against known transmission in simulated outbreaks. We also found a low proportion of epidemiologically supported case–contact pairs were identified in our real-world TB clusters. The specificity of all models was high, and a relatively high proportion of the total transmission events predicted by some models were true links, notably with TransPhylo, Outbreaker2, and Phybreak. Our findings may inform the choice of tools in TB transmission analyses and underscore the need for caution when interpreting transmission networks produced using probabilistic approaches.

Heterogeneity in the number of secondary tuberculosis (TB) cases per source case, the effective reproductive number, R, is important in modelling prevention strategies' impact on incidence.

We estimated mean R (Rm) and calculate the dispersion parameter of this distribution, k, using surveillance and genotyping data for U.S. cases during 2009–2018. We modelled transmission assuming cases in a cluster have matching genotypes and share characteristics related to geography, temporal proximity (i.e. serial interval) and time since U.S. arrival among non-U.S.-born persons.

Complete data were available for 55 330/85 958 cases. Varying the serial interval and geographic proximity used to derive clusters, we consistently estimated Rm<1.0 and k < 0.08; the low value of k indicates a small number of source cases produce a disproportionate number of secondary cases.

U.S. TB reproductive number has a highly skewed distribution, indicating a minority of source cases disproportionately contribute to transmission.

Hong Kong is an intermediate tuberculosis (TB) burden city in Asia Pacific with slow decline of case notification in the last decade. By 24-loci mycobacterial interspersed repetitive units – variable number of tandem repeats genotyping, we examined 534 Mycobacterium tuberculosis isolates collected from culture-positive hospitalised TB patients in a 1.7 million population geographic region in the city. Overall, 286 (75%) were classified as Beijing genotype, of which 216 (76%) and 59 (21%) belonged to modern and ancient sub-lineage, respectively. Only two cases were genetically clustered while spatial clustering was absent. Male gender, permanent residency in Hong Kong and born in Hong Kong or Mainland China were associated with Beijing genotype. The high prevalence of Beijing modern lineage was similar to that in East Asia, which reflected the pattern resulting from population migration. The paucity of clustering suggested that reactivation accounted for most of the TB disease cases, which was and echoed by observation that half were 60 years old or above, and the presence of co-morbid medical conditions. The predominance of reactivation TB cases in intermediate burden localities implies that the detection and control of latent TB infection would be the major challenge in achieving TB elimination.

Data on the prevalence of extrapulmonary tuberculosis (EPTB) patients are limited in many African countries including Malawi. We conducted a retrospective review of all histology reports for cancer suspected patients at Mzuzu Central Hospital (MZCH) between 2013 and 2018 to determine the proportion of EPTB cases among cancer suspected patients and characterised them epidemiologically. All reports with inconclusive findings were excluded. In total, 2214 reports were included in the review, 47 of which reported EPTB, representing 2.1% (95% CI 1.6−2.8). The incidence of EPTB was significantly associated with sex, age and HIV status. Men were more than twice (OR 2.1; 95% CI 1.2–3.9) as likely to have EPTB as women while those with HIV were more than six times (OR 6.4; 95% CI 1.7–24.8) as likely to have EPTB compared to those who were HIV-negative. EPTB demonstrated an inverse relationship with age. The highest proportion of EPTB was found from neck lymph nodes (10.3% (5.4–17.2)). A reasonable number of EPTB cases are diagnosed late or missed in Malawi's hospitals. There is a need for concerted efforts to increase EPTB awareness and likely come up with a policy to consider EPTB as a differential diagnosis in cancer suspected patients.

Despite considerable efforts to control tuberculosis (TB) among Ethiopian immigrants in Israel, an outbreak of TB among second-generation Ethiopian immigrants that involved native Israelis occurred between January 2011 and December 2019. The aim of this article is to report on this outbreak and discuss the patient and health system barriers that led to its propagation. Overall, 13 culture-positive TB patients were diagnosed in this outbreak. An additional 36 cases with identical mycobacterium tuberculosis genotypes were identified through cross-checking with the National TB Laboratory Registry. Among the 32 close contacts of the index case, 18 (56.3%) reported for screening and treatment of latent TB infection (LTBI) was recommended for 11 (61.1%) of them. However, none completed treatment and eight eventually developed TB. Of the 385 close contacts identified in this outbreak, 286 (74.3%) underwent contact investigation, 154 (53.8%) were recommended LTBI treatment, but only 26 (16.9%) completed the treatment. Routine contact investigation and treatment practice measures failed to contain the cascade of infection and disease, leading to the spread of the infecting strain of TB. This report highlights the challenges to identify the high-risk group and address barriers to care among such a vulnerable population.

Yukon Territory (YT) is a remote region in northern Canada with ongoing spread of tuberculosis (TB). To explore the utility of whole genome sequencing (WGS) for TB surveillance and monitoring in a setting with detailed contact tracing and interview data, we used a mixed-methods approach. Our analysis included all culture-confirmed cases in YT (2005–2014) and incorporated data from 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping, WGS and contact tracing. We compared field-based (contact investigation (CI) data + MIRU-VNTR) and genomic-based (WGS + MIRU-VNTR + basic case data) investigations to identify the most likely source of each person's TB and assessed the knowledge, attitudes and practices of programme personnel around genotyping and genomics using online, multiple-choice surveys (n = 4) and an in-person group interview (n = 5). Field- and genomics-based approaches agreed for 26 of 32 (81%) cases on likely location of TB acquisition. There was less agreement in the identification of specific source cases (13/22 or 59% of cases). Single-locus MIRU-VNTR variants and limited genetic diversity complicated the analysis. Qualitative data indicated that participants viewed genomic epidemiology as a useful tool to streamline investigations, particularly in differentiating latent TB reactivation from the recent transmission. Based on this, genomic data could be used to enhance CIs, focus resources, target interventions and aid in TB programme evaluation.

Tuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131 Mycobacterium tuberculosis (M.tb) DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of the katG, inhA and rpoB genes and RDRio sublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRio deletion was observed in 42 (32%) of the M.tb isolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%) M.tb isolates, we found mutations associated with rifampicin (RIF) resistance in rpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance in katG and inhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in the rpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.

Few studies have used genomic epidemiology to understand tuberculosis (TB) transmission in rural and remote settings – regions often unique in history, geography and demographics. To improve our understanding of TB transmission dynamics in Yukon Territory (YT), a circumpolar Canadian territory, we conducted a retrospective analysis in which we combined epidemiological data collected through routine contact investigations with clinical and laboratory results. Mycobacterium tuberculosis isolates from all culture-confirmed TB cases in YT (2005–2014) were genotyped using 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) and compared to each other and to those from the neighbouring province of British Columbia (BC). Whole genome sequencing (WGS) of genotypically clustered isolates revealed three sustained transmission networks within YT, two of which also involved BC isolates. While each network had distinct characteristics, all had at least one individual acting as the probable source of three or more culture-positive cases. Overall, WGS revealed that TB transmission dynamics in YT are distinct from patterns of spread in other, more remote Northern Canadian regions, and that the combination of WGS and epidemiological data can provide actionable information to local public health teams.

We investigated the distribution of comorbidities among adult tuberculosis (TB) patients in Chiapas, the poorest Mexican state, with a high presence of indigenous population, and a corridor for migrants from Latin America. Secondary analysis on 5508 new adult TB patients diagnosed between 2010 and 2014 revealed that the most prevalent comorbidities were diabetes mellitus (DM; 19.1%) and undernutrition (14.4%). The prevalence of DM in these TB patients was significantly higher among middle aged (41–64 years) compared with older adults (⩾65 years) (38.6% vs. 23.2%; P < 0.0001). The prevalence of undernutrition was lower among those with DM, and higher in communities with high indigenous presence. Immigrants only comprised 2% of all TB cases, but were more likely to have unfavourable TB treatment outcomes (treatment failure, death and default) when compared with those born in Chiapas (29.5% vs. 11.1%; P < 0.05). Unfavourable TB outcomes were also more prevalent among the TB patients with undernutrition, HIV or older age, but not DM (P < 0.05). Our study in Chiapas illustrates the challenges of other regions worldwide where social (e.g. indigenous origin, poverty, migration) and host factors (DM, undernutrition, HIV, older age) are associated with TB. Further understanding of these critical factors will guide local policy makers and health providers to improve TB management.

Following an extensive contact tracing exercise at a school in a London borough with one of highest tuberculosis (TB) rates in England, we estimated the background prevalence of latent TB infection to be significantly less than the widely accepted 10%. We screened 271 pupils aged 14–15 years in two groups: 96 pupils in group 1 had significant exposure (>8 h/week in the same room) to a case of infectious TB and 175 in group 2 who had minimal exposure. In group 1, 26% were diagnosed with latent or active TB, compared to 6.3% in group 2. Risk factors for TB infection (e.g. previous exposure or link to high-prevalence communities) were analysed using a cohort study design. In the univariable analysis only being in contact group 1 was statistically significantly associated with being a case (OR 5.25, 95%, P < 0.001). In the multivariable model contact group 1 remained significantly associated with being a case (adjusted OR 4.40, P = 0.001). We concluded that the 6.3% yield of TB infection in contact group 2 is either similar to or higher than the background prevalence rate of latent TB infection (LTBI) in this high TB prevalence London borough. Other parts of England with lower TB prevalence are likely to have even lower LTBI rates.

We evaluated and compared the completeness, timeliness, simplicity, usefulness and flexibility between the former National Tuberculosis (TB) Surveillance System (NTBSS) and the newer Computerised Infectious Disease Reporting System (CIDR). Completeness was assessed by examining the field completion of key variables and median time from diagnosis to notification was calculated to evaluate timeliness. Differences between the two systems on completeness and timeliness were statistically assessed using χ2 and Wilcoxon rank-sum test, respectively. An online questionnaire on simplicity, flexibility and usefulness was sent to key stakeholders. Time and diagnosis-related variables were more complete in NTBSS, while variables on drug susceptibility, HIV and laboratory tests were more complete in CIDR (P < 0.05). The median time notification interval increased significantly in CIDR (P < 0.05). Stakeholders thought that CIDR is simpler (37.5%), more useful (41.7%) and more flexible (29.2%) than NTBSS. This study demonstrated that CIDR did not improve data completeness and decreased timeliness of notification. Simplicity, usefulness and flexibility were improved but qualitative methods should be applied to further explore these results.

The diagnosis and control of Mycobacterium bovis infection (bovine tuberculosis: TB) continues to present huge challenges to the British cattle industry. A clearer understanding of the magnitude and duration of immune response to M. bovis infection in the European badger (Meles meles) – a wildlife maintenance host – may assist with the future development of diagnostic tests, and vaccination and disease management strategies. Here, we analyse 5280 diagnostic test results from 550 live wild badgers from a naturally-infected population to investigate whether one diagnostic test (a gamma interferon release [IFNγ] assay, n = 550 tests) could be used to predict future positive results on two other tests for the same disease (a serological test [n = 2342 tests] and mycobacterial culture [n = 2388 tests]) and hence act as an indicator of likely bacterial excretion or disease progression. Badgers with the highest IFNγ optical density (OD) values were most likely to subsequently test positive on both serological and culture tests, and this effect was detectable for up to 24 months after the IFNγ test. Furthermore, the higher the original IFNγ OD value, the greater the chance that a badger would subsequently test positive using serology. Relationships between IFNγ titres and mycobacterial culture results from different types of clinical sample suggest that the route of infection may affect the magnitude of immune response in badgers. These findings identify further value in the IFNγ test as a useful research tool, as it may help us to target studies at animals and groups that are most likely to succumb to more progressive disease.

The purpose of this study was to develop a method for identifying newly diagnosed tuberculosis (TB) patients at risk for TB adverse events in Tamaulipas, Mexico. Surveillance data between 2006 and 2013 (8431 subjects) was used to develop risk scores based on predictive modelling. The final models revealed that TB patients failing their treatment regimen were more likely to have at most a primary school education, multi-drug resistance (MDR)-TB, and few to moderate bacilli on acid-fast bacilli smear. TB patients who died were more likely to be older males with MDR-TB, HIV, malnutrition, and reporting excessive alcohol use. Modified risk scores were developed with strong predictability for treatment failure and death (c-statistic 0·65 and 0·70, respectively), and moderate predictability for drug resistance (c-statistic 0·57). Among TB patients with diabetes, risk scores showed moderate predictability for death (c-statistic 0·68). Our findings suggest that in the clinical setting, the use of our risk scores for TB treatment failure or death will help identify these individuals for tailored management to prevent these adverse events. In contrast, the available variables in the TB surveillance dataset are not robust predictors of drug resistance, indicating the need for prompt testing at time of diagnosis.

Mycobacterial diseases are prevalent in cancer and rheumatoid arthritis (RA) patients, especially those receiving tumor necrosis factor-α inhibitor (TNFi). However, the impact of cancer development on the risk of mycobacterial diseases among RA patients is unknown. Data from the Taiwan National Health Insurance Research Database were used to conduct a retrospective study to assess the occurrence of mycobacterial diseases in RA patients developing cancer (cancer-positive), those using TNFi (TNFi-exposure), those with cancer and using TNFi (cancer-TNFi-comb), and those without cancer and not using TNFi (cancer-TNFi-free). Cancer and TNFi exposure were time-dependent, and independent risk factors of mycobacterial diseases were assessed by Cox regression. Among 1344 RA patients diagnosed during 2000–2013, 68 (5·1%) developed cancer before their end points. The incidence rates of mycobacterial diseases in the cancer-positive (n = 56), TNFi-exposure (n = 290), cancer-TNFi-comb (n = 12), and cancer-TNFi-free (n = 986) subgroups were 6·7, 2·0, 7·6, and 1·3 per 1000 person-years, respectively. As compared with the cancer-TNFi-free group, the risk for mycobacterial diseases increased for the TNFi-exposure group (adjusted HR = 3·6, 95% confidence interval (95% CI) 1·1–11·5, P = 0·032) and remained high for cancer-positive (adjusted HR = 14·6, 95% CI 3·3–63·7, P < 0·001) after adjustment. This study suggested that cancer development increased the risk of mycobacterial diseases in RA patients, and risk assessment for this subgroup should be considered.

Tuberculosis (TB) mortality rates in the USA fell rapidly from 1910 to 1933. However, during this period, racial disparities in TB mortality in the nation's expanding cities grew. Because of long delays between infection and disease, TB mortality is a poor indicator of short-term changes in transmission. We estimated the annual risk of TB infection (ARTI) in 11 large US cities to understand whether rising inequality in mortality reflected rising inequality in ARTI using city-level TB mortality data compiled by the US Department of Commerce from 1910 to 1933. We estimated ARTI for African-Americans and whites using pediatric extrapulmonary TB mortality data for African-Americans and whites in our panel of cities. We also estimated age-adjusted pulmonary TB mortality rates for these cities. We find that the ratio of ARTI for African-Americans vs. whites increased from 2·1 (95% CI = 1·7, 2·4) in 1910 to 4·2 (95% CI = 3·4, 5·2) in 1933. This change mirrored the increasing inequality in age-adjusted pulmonary TB mortality during this period. These findings may reflect the combined effects of migration, inequality in access to care, increasing population density, and racial residential segregation in northern cities during this period.

In the development of vaccines for tuberculosis (TB), the combination of the will, funding, scientific rigor, new tools, refined animal models and improved clinical trial designs are all converging at an opportune moment. The lack of optimism that has surrounded the likelihood for finding novel TB vaccines has resulted from a lack of correlates of vaccine-induced protection, a lack of tool candidate vaccines to probe the immunologic space, which may be needed, and the negative result of one recent trial. A vaccine for TB that can be delivered at a reasonable cost to the marketplace will have greater impact on the incidence of new cases of TB than any intervention in world history. Now is the time to increase resources, both financial and human intellectual capacity, for a global tuberculosis vaccine effort.

We compared the cost-effectiveness (CE) of an active case-finding (ACF) programme for household contacts of tuberculosis (TB) cases enrolled in first-line treatment to routine passive case-finding (PCF) within an established national TB programme in Peru. Decision analysis was used to model detection of TB in household contacts through: (1) self-report of symptomatic cases for evaluation (PCF), (2) a provider-initiated ACF programme, (3) addition of an Xpert MTB/RIF diagnostic test for a single sputum sample from household contacts, and (4) all strategies combined. CE was calculated as the incremental cost-effectiveness ratio (ICER) in terms of US dollars per disability-adjusted life years (DALYs) averted. Compared to PCF alone, ACF for household contacts resulted in an ICER of $2155 per DALY averted. The addition of the Xpert MTB/RIF diagnostic test resulted in an ICER of $3275 per DALY averted within a PCF programme and $3399 per DALY averted when an ACF programme was included. Provider-initiated ACF of household contacts in an urban setting of Lima, Peru can be highly cost-effective, even including costs to seek out contacts and perform an Xpert/MTB RIF test. ACF including Xpert MTB/RIF was not cost-effective if TB cases detected had high rates of default from treatment or poor outcomes.

Tuberculosis (TB) affects people globally and is being reconsidered as a serious public health problem in China. Reliable forecasting is useful for the prevention and control of TB. This study proposes a hybrid model combining autoregressive integrated moving average (ARIMA) with a nonlinear autoregressive (NAR) neural network for forecasting the incidence of TB from January 2007 to March 2016. Prediction performance was compared between the hybrid model and the ARIMA model. The best-fit hybrid model was combined with an ARIMA (3,1,0) × (0,1,1)12 and NAR neural network with four delays and 12 neurons in the hidden layer. The ARIMA-NAR hybrid model, which exhibited lower mean square error, mean absolute error, and mean absolute percentage error of 0·2209, 0·1373, and 0·0406, respectively, in the modelling performance, could produce more accurate forecasting of TB incidence compared to the ARIMA model. This study shows that developing and applying the ARIMA-NAR hybrid model is an effective method to fit the linear and nonlinear patterns of time-series data, and this model could be helpful in the prevention and control of TB.

Tuberculosis (TB) in older people is a significant public health problem in low TB-incidence countries. Older persons have increased TB incidence, higher reactivation and mortality. A delay in diagnosis and initiation of TB treatment in patients with atypical clinical and radiological features is a significant factor of widespread transmission. This study aimed to evaluate the cost-effectiveness of interferon-gamma release assays [IGRAs; QuantiFERON®-TB Gold In-Tube (QFT) and T-SPOT®.TB (T-SPOT)] compared to the tuberculin skin test (TST) and chest X-ray (CXR) examination for TB screening for nursing homes. Decision trees and Markov models were constructed using a societal perspective on a lifetime horizon. Seven strategies: no screening, TST, QFT, T-SPOT, TST followed by QFT, TST followed by T-SPOT, and CXR were considered. QFT [US$ 401·9, 4·36 707 QALY (year 2014 values)] was the most cost-effective at the willingness-to-pay level of US$ 50 000/QALY gained. TST followed by QFT was the most cost-effective in residents with comorbidities. CXR was less cost-effective. Cost-effectiveness was sensitive to latent TB infection (LTBI) rate and bacillus Calmette-Guérin vaccination rate. Effective LTBI screening using IGRA is recommended to prevent TB transmission not only in nursing homes but also in local communities in low-incidence countries.