Tuberculosis: Novel Insights and Approaches to Tackle an Ancient Disease

A special issue of Tropical Medicine and Infectious Disease (ISSN 2414-6366). This special issue belongs to the section "Infectious Diseases".

Deadline for manuscript submissions: closed (29 February 2024) | Viewed by 18020

Special Issue Editor


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Guest Editor
School of Public Health and Preventive Medicine, Monash University, Melbourne 3004, Australia
Interests: tuberculosis; epidemiology; mathematical modelling; prevention; detection

Special Issue Information

Dear Colleagues,

Tuberculosis (TB) has plagued humankind throughout history. Its causative agent (mycobacterium tuberculosis) was first identified in 1882 and yet, around 140 years later, TB is still estimated to affect around ten million people worldwide each year. The availability of effective vaccines and treatments has been insufficient to control TB and it is predicted that disease elimination will not be achieved in the coming decades without fundamentally rethinking our approach to control.

Innovative tools and control approaches have emerged in recent years, providing great hope for global TB control. These include improved detection technologies and treatment regimens, as well as promising vaccine candidates. Ambitious screening programs and promising clinical trials related to TB detection and prevention have also been implemented in various regions, including Vietnam, Canada, the Marshall Islands, and Ghana.

However, a better understanding of TB epidemiology is critically needed to ensure that novel tools and approaches are used efficiently and to maximise their impact on the burden of TB. Many aspects of the disease remain poorly understood, including the impact of comorbidities such as diabetes or HIV and the risk represented by latent TB infection. The true extent of the disease is also unknown in most places due to imperfect case detection and reporting issues.

This Special Issue focuses on highlighting recent findings in TB epidemiology that provide key insights for future TB control. We invite submissions of reports on a wide range of studies, including local investigations, international collaborations, systematic reviews, statistical analyses, and mathematical modelling analyses.

Dr. Romain Ragonnet
Guest Editor

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Keywords

  • tuberculosis
  • epidemiology
  • TB control
  • TB prevention
  • mathematical modelling of TB
  • active case-finding
  • drug-resistant TB
  • TB vaccines

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Published Papers (8 papers)

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Research

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16 pages, 2754 KiB  
Article
Effectiveness of Using AI-Driven Hotspot Mapping for Active Case Finding of Tuberculosis in Southwestern Nigeria
by Abiola Alege, Sumbul Hashmi, Rupert Eneogu, Vincent Meurrens, Anne-Laure Budts, Michael Pedro, Olugbenga Daniel, Omokhoudu Idogho, Austin Ihesie, Matthys Gerhardus Potgieter, Obioma Chijioke Akaniro, Omosalewa Oyelaran, Mensah Olalekan Charles and Aderonke Agbaje
Trop. Med. Infect. Dis. 2024, 9(5), 99; https://doi.org/10.3390/tropicalmed9050099 - 29 Apr 2024
Viewed by 1793
Abstract
Background: Nigeria is among the top five countries that have the highest gap between people reported as diagnosed and estimated to have developed tuberculosis (TB). To bridge this gap, there is a need for innovative approaches to identify geographical areas at high [...] Read more.
Background: Nigeria is among the top five countries that have the highest gap between people reported as diagnosed and estimated to have developed tuberculosis (TB). To bridge this gap, there is a need for innovative approaches to identify geographical areas at high risk of TB transmission and targeted active case finding (ACF) interventions. Leveraging community-level data together with granular sociodemographic contextual information can unmask local hotspots that could be otherwise missed. This work evaluated whether this approach helps to reach communities with higher numbers of undiagnosed TB. Methodology: A retrospective analysis of the data generated from an ACF intervention program in four southwestern states in Nigeria was conducted. Wards (the smallest administrative level in Nigeria) were further subdivided into smaller population clusters. ACF sites and their respective TB screening outputs were mapped to these population clusters. This data were then combined with open-source high-resolution contextual data to train a Bayesian inference model. The model predicted TB positivity rates on the community level (population cluster level), and these were visualised on a customised geoportal for use by the local teams to identify communities at high risk of TB transmission and plan ACF interventions. The TB positivity yield (proportion) observed at model-predicted hotspots was compared with the yield obtained at other sites identified based on aggregated notification data. Results: The yield in population clusters that were predicted to have high TB positivity rates by the model was at least 1.75 times higher (p-value < 0.001) than the yield in other locations in all four states. Conclusions: The community-level Bayesian predictive model has the potential to guide ACF implementers to high-TB-positivity areas for finding undiagnosed TB in the communities, thus improving the efficiency of interventions. Full article
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16 pages, 1026 KiB  
Article
Capturing Recent Mycobacterium tuberculosis Infection by Tuberculin Skin Test vs. Interferon-Gamma Release Assay
by Jesús Gutierrez, Mary Nsereko, LaShaunda L. Malone, Harriet Mayanja-Kizza, Hussein Kisingo, W. Henry Boom, Charles M. Bark and Catherine M. Stein
Trop. Med. Infect. Dis. 2024, 9(4), 81; https://doi.org/10.3390/tropicalmed9040081 - 11 Apr 2024
Viewed by 1570
Abstract
Reductions in tuberculosis (TB) incidence require identification of individuals at high risk of developing active disease, such as those with recent Mycobacterium tuberculosis (Mtb) infection. Using a prospective household contact (HHC) study in Kampala, Uganda, we diagnosed new Mtb infection using [...] Read more.
Reductions in tuberculosis (TB) incidence require identification of individuals at high risk of developing active disease, such as those with recent Mycobacterium tuberculosis (Mtb) infection. Using a prospective household contact (HHC) study in Kampala, Uganda, we diagnosed new Mtb infection using both the tuberculin skin test (TST) and interferon-gamma release assay (IGRA). Our study aimed to determine if the TST adds additional value to the characterization of IGRA converters. We identified 13 HHCs who only converted the IGRA (QFT-only converters), 39 HHCs who only converted their TST (TST-only converters), and 24 HHCs who converted both tests (QFT/TST converters). Univariate analysis revealed that TST-only converters were older. Additionally, increased odds of TST-only conversion were associated with older age (p = 0.02) and crowdedness (p = 0.025). QFT/TST converters had higher QFT quantitative values at conversion than QFT-only converters and a bigger change in TST quantitative values at conversion than TST-only converters. Collectively, these data indicate that TST conversion alone likely overestimates Mtb infection. Its correlation to older age suggests an “environmental” boosting response due to prolonged exposure to environmental mycobacteria. This result also suggests that QFT/TST conversion may be associated with a more robust immune response, which should be considered when planning vaccine studies. Full article
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15 pages, 1743 KiB  
Article
Ensuring Continuity of Tuberculosis Care during Social Distancing through Integrated Active Case Finding at COVID-19 Vaccination Events in Vietnam: A Cohort Study
by Luong Van Dinh, Luan Nguyen Quang Vo, Anja Maria Christine Wiemers, Hoa Binh Nguyen, Hoa Quynh Vu, Huong Thi Lan Mo, Lan Phuong Nguyen, Nga Thi Thuy Nguyen, Thuy Thi Thu Dong, Khoa Tu Tran, Thi Minh Ha Dang, Lan Huu Nguyen, Anh Thu Pham, Andrew James Codlin and Rachel Jeanette Forse
Trop. Med. Infect. Dis. 2024, 9(1), 26; https://doi.org/10.3390/tropicalmed9010026 - 22 Jan 2024
Viewed by 2885
Abstract
COVID-19 significantly disrupted tuberculosis (TB) services in Vietnam. In response, the National TB Program (NTP) integrated TB screening using mobile chest X-rays into COVID-19 vaccination events. This prospective cohort study evaluated the integrated model’s yield, treatment outcomes, and costs. We further fitted regressions [...] Read more.
COVID-19 significantly disrupted tuberculosis (TB) services in Vietnam. In response, the National TB Program (NTP) integrated TB screening using mobile chest X-rays into COVID-19 vaccination events. This prospective cohort study evaluated the integrated model’s yield, treatment outcomes, and costs. We further fitted regressions to identify risk factors and conduct interrupted time-series analyses in the study area, Vietnam’s eight economic regions, and at the national level. At 115 events, we conducted 48,758 X-ray screens and detected 174 individuals with TB. We linked 89.7% to care, while 92.9% successfully completed treatment. The mean costs per person diagnosed with TB was $547. TB risk factors included male sex (aOR = 6.44, p < 0.001), age of 45–59 years (aOR = 1.81, p = 0.006) and ≥60 years (aOR = 1.99, p = 0.002), a history of TB (aOR = 7.96, p < 0.001), prior exposure to TB (aOR = 3.90, p = 0.001), and symptomatic presentation (aOR = 2.75, p < 0.001). There was a significant decline in TB notifications during the Delta wave and significant increases immediately after lockdowns were lifted (IRR(γ1) = 5.00; 95%CI: (2.86, 8.73); p < 0.001) with a continuous upward trend thereafter (IRR(γ2) = 1.39; 95%CI: (1.22, 1.38); p < 0.001). Similar patterns were observed at the national level and in all regions but the northeast region. The NTP’s swift actions and policy decisions ensured continuity of care and led to the rapid recovery of TB notifications, which may serve as blueprint for future pandemics. Full article
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12 pages, 2311 KiB  
Article
Comparing Catastrophic Costs: Active vs. Passive Tuberculosis Case Finding in Urban Vietnam
by Luong V. Dinh, Anja M. C. Wiemers, Rachel J. Forse, Yen T. H. Phan, Andrew J. Codlin, Kristi Sidney Annerstedt, Thuy T. T. Dong, Lan Nguyen, Thuong H. Pham, Lan H. Nguyen, Ha M. T. Dang, Mac H. Tuan, Phuc Thanh Le, Knut Lonnroth, Jacob Creswell, Amera Khan, Beatrice Kirubi, Hoa B. Nguyen, Nhung V. Nguyen and Luan N. Q. Vo
Trop. Med. Infect. Dis. 2023, 8(9), 423; https://doi.org/10.3390/tropicalmed8090423 - 23 Aug 2023
Cited by 1 | Viewed by 2661
Abstract
Active case finding (ACF) is a strategy that aims to identify people with tuberculosis (TB) earlier in their disease. This outreach approach may lead to a reduction in catastrophic cost incurrence (costs exceeding 20% of annual household income), a main target of WHO’s [...] Read more.
Active case finding (ACF) is a strategy that aims to identify people with tuberculosis (TB) earlier in their disease. This outreach approach may lead to a reduction in catastrophic cost incurrence (costs exceeding 20% of annual household income), a main target of WHO’s End TB Strategy. Our study assessed the socio-economic impact of ACF by comparing patient costs in actively and passively detected people with TB. Longitudinal patient cost surveys were prospectively fielded for people with drug-sensitive pulmonary TB, with 105 detected through ACF and 107 passively detected. Data were collected in four Vietnamese cities between October 2020 and March 2022. ACF reduced pre-treatment (USD 10 vs. 101, p < 0.001) and treatment costs (USD 888 vs. 1213, p < 0.001) in TB-affected individuals. Furthermore, it reduced the occurrence of job loss (15.2% vs. 35.5%, p = 0.001) and use of coping strategies (28.6% vs. 45.7%, p = 0.004). However, catastrophic cost incurrence was high at 52.8% and did not differ between cohorts. ACF did not significantly decrease indirect costs, the largest contributor to catastrophic costs. ACF reduces costs but cannot sufficiently reduce the risk of catastrophic costs. As income loss is the largest driver of costs during TB treatment, social protection schemes need to be expanded. Full article
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12 pages, 1567 KiB  
Article
Spatial Analysis of Tuberculosis Patient Flow in a Neglected Region of Northern Brazil
by Cristal Ribeiro Mesquita, Marília Lima da Conceição, Rafael Aleixo Coelho de Oliveira, Emilyn Costa Conceição, Juliana Conceição Dias Garcez, Ianny Ferreira Raiol Sousa, Luana Nepomuceno Gondim Costa Lima, Karla Valéria Batista Lima and Ricardo José de Paula Souza e Guimarães
Trop. Med. Infect. Dis. 2023, 8(8), 397; https://doi.org/10.3390/tropicalmed8080397 - 2 Aug 2023
Cited by 1 | Viewed by 1631
Abstract
Tuberculosis (TB) is still considered a priority due to its high incidence rate in Brazil. In this context, we aimed to evaluate the flow of care between the municipalities of patients diagnosed with TB through notification forms of the Information System for Diseases [...] Read more.
Tuberculosis (TB) is still considered a priority due to its high incidence rate in Brazil. In this context, we aimed to evaluate the flow of care between the municipalities of patients diagnosed with TB through notification forms of the Information System for Diseases and Notifications (SINAN) in a neglected region of Northern Brazil, Ilha do Marajó, state of Para. For this, we performed a descriptive, retrospective study on data obtained from the National Register of Health Establishments and SINAN from 2013 to 2018. We used Pearson’s Chi-square and G Test with p-value < 0.05 for descriptive statistics and spatial analysis technique on flow network analysis. Of the 749 cases, 16.5% were notified in another municipality that was not the patient’s residence. Regarding diagnostic methods, a positive bacterioscopy was adopted for 56% of the patients; culture was not performed for 82% of cases. Histopathological examination was not performed in 90% of the individuals. Rapid molecular test (RMT) was performed in only six (5%) cases. The region needs greater attention focused on diagnostic tests, suggesting that the introduction of RMT and culture by Ogawa-Kudoh could improve the region’s health network to minimise patient displacement and thus avoid the increase in the transmission chain of TB. Full article
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12 pages, 300 KiB  
Article
Adherence and Toxicity during the Treatment of Latent Tuberculous Infection in a Referral Center in Spain
by Juan David Puyana Ortiz, Andrea Carolina Garcés Rodríguez, María Luisa Aznar, Juan Espinosa Pereiro, Adrián Sánchez-Montalvá, Joan Martínez-Campreciós, Nuria Saborit, José Ángel Rodrigo-Pendás, Guadalupe García Salgado, Claudia Broto Cortes, Nuria Serre Delcor, Inés Oliveira, Begoña Treviño Maruri, Diana Pou Ciruelo, Fernando Salvador, Pau Bosch-Nicolau, Irene Torrecilla-Martínez, Ricardo Zules-Oña, María Teresa Tórtola Fernández and Israel Molina
Trop. Med. Infect. Dis. 2023, 8(7), 373; https://doi.org/10.3390/tropicalmed8070373 - 19 Jul 2023
Cited by 1 | Viewed by 1553
Abstract
The screening and treatment of latent tuberculosis infection (LTBI) in countries with a low incidence of TB is a key strategy for the elimination of tuberculosis (TB). However, treatment can result in adverse events (AEs) and have poor adherence. This study aimed to [...] Read more.
The screening and treatment of latent tuberculosis infection (LTBI) in countries with a low incidence of TB is a key strategy for the elimination of tuberculosis (TB). However, treatment can result in adverse events (AEs) and have poor adherence. This study aimed to describe treatment outcomes and AEs for LTBI patients at two departments in Vall d’Hebron University Hospital in Barcelona, Spain. A retrospective study was conducted on all persons treated for LTBI between January 2018 and December 2020. Variables collected included demographics, the reason for LTBI screening and treatment initiation, AEs related to treatment, and treatment outcome. Out of 261 persons who initiated LTBI treatment, 145 (55.6%) were men, with a median age of 42.1 years. The indications for LTBI screening were household contact of a TB case in 96 (36.8%) persons, immunosuppressive treatment in 84 (32.2%), and recently arrived migrants from a country with high TB incidence in 81 (31.0%). Sixty-three (24.1%) persons presented at least one AE during treatment, and seven (2.7%) required definitive discontinuation of treatment. In the multivariate analysis, AE development was more frequent in those who started LTBI treatment due to immunosuppression. Overall, 226 (86.6%) completed treatment successfully. We concluded that LTBI screening and treatment groups had different risks for adverse events and treatment outcomes. Persons receiving immunosuppressive treatment were at higher risk of developing AEs, and recently arrived immigrants from countries with a high incidence of TB had greater LTFU. A person-centered adherence and AE management plan is recommended. Full article
10 pages, 404 KiB  
Article
Comparison of Xpert MTB/RIF Ultra Results of Stool and Sputum in Children with Presumptive Tuberculosis in Southern Ethiopia
by Yohannes Babo, Bihil Seremolo, Mamush Bogale, Ahmed Bedru, Yasin Wabe, Haba Churako, Alemu Bilat, Tamiru Degaga, Petra de Haas, Edine Tiemersma and Degu Jerene
Trop. Med. Infect. Dis. 2023, 8(7), 350; https://doi.org/10.3390/tropicalmed8070350 - 30 Jun 2023
Cited by 4 | Viewed by 2749
Abstract
The introduction of stool as a readily obtainable sample and the recently developed simple one-step (SOS) stool processing method on Xpert MTB/RIF Ultra (Xpert Ultra) offer an opportunity for TB diagnosis in children. We conducted this study in secondary health facilities in Ethiopia, [...] Read more.
The introduction of stool as a readily obtainable sample and the recently developed simple one-step (SOS) stool processing method on Xpert MTB/RIF Ultra (Xpert Ultra) offer an opportunity for TB diagnosis in children. We conducted this study in secondary health facilities in Ethiopia, which are the first-level referral facilities for childhood TB diagnosis and treatment, with the aim to determine if stool-based TB diagnosis can be performed with a reasonable level of concordance with sputum tests using Xpert MTB/RIF Ultra. Eligible children 0–14 years old with presumptive pulmonary TB were asked to provide stools in addition to routinely requested sputum samples. We determined the level of agreement between the stool and sputum test results. Of the 373 children included in the study, 61% were <5 years of age and 56% were male. Thirty-six children (9.7%) were diagnosed with TB, and all started treatment. The rate of concordance between stool and sputum was high, with a kappa value of 0.83 (p < 0.001). There were more Xpert Ultra positive results on stool (n = 27 (7.2%)) than on sputum/NGA (n = 23 (6.2%)). Laboratories in secondary hospitals can perform stool-based TB diagnosis in children, with high concordance between stool and sputum test results reaffirming the applicability of the SOS stool method. Full article

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10 pages, 409 KiB  
Brief Report
The Cost-Effectiveness of the BEAT-TB Regimen for Pre-Extensively Drug-Resistant TB
by Malaisamy Muniyandi, Paranchi Murugesan Ramesh, William A. Wells, Umesh Alavadi, Suvanand Sahu and Chandrasekaran Padmapriyadarsini
Trop. Med. Infect. Dis. 2023, 8(8), 411; https://doi.org/10.3390/tropicalmed8080411 - 11 Aug 2023
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Abstract
Objective: To measure the economic impacts of the longer pre-XDR-TB treatment regimen and the shorter BEAT-TB India regimen. Methods: In the current study, the economic impacts of the current 18-month pre-XDR-TB treatment regimen and the 6–9 month BEAT-TB regimen were evaluated using an [...] Read more.
Objective: To measure the economic impacts of the longer pre-XDR-TB treatment regimen and the shorter BEAT-TB India regimen. Methods: In the current study, the economic impacts of the current 18-month pre-XDR-TB treatment regimen and the 6–9 month BEAT-TB regimen were evaluated using an economic model via a decision tree analysis from a societal perspective. The incremental costs and quality-adjusted life years (QALYs) gained from the introduction of the BEAT-TB regimen for pre-XDR-TB patients were estimated. Results: For a cohort of 1000 pre-XDR-TB patients, we found that the BEAT-TB India regimen yielded higher undiscounted life years (40,548 vs. 21,009) and more QALYs gained (27,633 vs. 15,812) than the 18-month regimen. The BEAT-TB India regimen was found to be cost-saving, with an incremental cost of USD −128,651 when compared to the 18-month regimen. The current analysis did not consider the possibility of reduced TB recurrence after use of the BEAT-TB regimen, so it might have under-estimated the benefits. Conclusion: As a lower-cost intervention with improved health outcomes, the BEAT-TB India regimen is dominant when compared to the 18-month regimen. Full article
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