Outbreak Of Tuberculosis Research Articles

A prolonged outbreak of tuberculosis associated with an intellectual disability daycentre in Ireland

Abstract One of the factors impeding tuberculosis elimination in low burden countries is its persistence and concentration in vulnerable populations. This is a complex, prolonged Tuberculosis (TB) outbreak in a daycentre for adults with intellectual disability in Ireland. This is a particularly vulnerable population with special considerations for Public Health (PH) management. There are eight cases of active TB, 46 cases of Latent TB Infection (LTBI) and a cumulative total of 116 contacts associated with this outbreak, with diagnosis spanning 15 years. The last three cases were identical on Whole Genome Sequencing. The index case was an Irish-born, Caucasian, social care worker, with smear positive pulmonary TB, who was symptomatic in the facility for three months prior to diagnosis. Case 2 was a household contact of the index case and the other 6 cases were Service Users (SUs) at the facility. At least five of the subsequent seven cases are secondary cases of the index case. Significant to this outbreak was the change in Irish guidance, 2010, relating to the management of contacts of cases. Following the notification of the most recent case, July 2023, the Outbreak Control Team decided a retrospective review be conducted of all SU contacts of the seven cases associated with the facility. The contacts were stratified according to hierarchical risk. A total of six contacts met the criteria for review and offered screening, re-screening or treatment as appropriate. In this outbreak 21.8% of the total contacts and 16.1% of SU contacts completed treatment for LTBI. The significance of this outbreak lies in its duration, infectivity of the index case and particular vulnerabilities of the SUs. There were issues with overcrowding and difficulties in relation to symptom recognition, diagnosis and treatment. The PH team tailored their approach to meet the SU needs, demonstrating the importance of person-centred contact tracing in the disruption of transmission. Key messages • A factor impeding tuberculosis elimination in low burden countries is it’s persistence and concentration in vulnerable populations. • Adapting a patient-centred approach to contact tracing can lead to higher participation rate and the disruption of infection transmission.

Characteristics of smear-positive pulmonary tuberculosis with normal chest radiographic findings during a tuberculosis outbreak in northeast Malaysia: A cross-sectional study.

Tuberculosis (TB) remains a highly prevalent disease in Malaysia. Early identification using cost-effective methods such as chest radiography can reduce the health burden of a TB epidemic. However, normal chest radiographic findings are common. This study aimed to evaluate the characteristics of smear-positive pulmonary TB with normal chest radiographic findings during an outbreak. A cross-sectional study was conducted by reviewing the medical records of 56 pulmonary TB cases registered at Kodiang Health Clinic from April to October 2022. Smear-negative and extrapulmonary TB cases were excluded. Relevant information was extracted from the medical records and recorded in a case report form for data management and analysis. Approximately 60.7% of the cases had symptoms lasting >2 weeks, and 89.3% showed abnormal findings upon clinical examination. Additionally, 73.2% had sputum acid-fast bacilli counts of ≥1+, and the sputum Mycobacterium tuberculosis culture and sensitivity test findings were positive in 82.1% of the cases. The proportion of smear-positive pulmonary TB with normal chest radiographic findings was 42.9%. The factors associated with smear-positive pulmonary TB with normal chest radiographic findings included being under 18 years old (P=0.021), being a student (P=0.010), being single (P=0.012) and being asymptomatic (P=0.04). Normal chest radiographic findings may lead to a misdiagnosis of smear-positive pulmonary TB, especially during an outbreak. Therefore, active case detection among close contacts with risk factors for normal radiographic findings should consider additional supportive tests.

Genomic and Spatial Analysis on the Recent Transmission of Mycobacterium tuberculosis in Eastern China: A 10-Year Retrospective Population-Based Study.

Understanding the mode of Mycobacterium tuberculosis (M. tuberculosis) transmission is crucial for disease prevention and control. Compared to traditional genotyping methods, whole genome sequencing (WGS) provides higher resolution and comprehensive genetic information, enabling the tracing of infection sources and determining of transmission routes to resolve extensive tuberculosis (TB) outbreaks. We conducted a ten-year study on the transmission of M. tuberculosis in a population in eastern China. We selected Lianyungang, an eastern city in China, as the study site. Patients diagnosed with active pulmonary TB from 2011 to 2020 were enrolled as the study subjects. We isolated and sequenced 2252 M. tuberculosis. Strains with pairwise genetic distances of less than 12 single nucleotide polymorphisms were defined as genomic clusters and which were considered recent transmissions. Kernel density estimation and K-function analysis were applied to explore the spatial distribution of recently transmitted strains. After excluding non-tuberculous mycobacteria and duplicated samples, 2114 strains were included in the final analysis. These strains comprised lineage 2 (1593, 75.35%) and 4 (521, 24.65%). There were 672 clustered strains, with a recent transmission rate of 31.79%. The logistic regression model showed that the risk of recent transmission was high in students [adjusted odds ratio (aOR): 2.68, 95% confidence interval (CI): 1.63-4.49, P<0.001] and people infected with L2.2.1 strains (aOR: 1.59, 95% CI: 1.20-2.12). Higher spatial aggregation of TB transmission has been concentrated in Haizhou, Donghai, and Guanyun for the past 10 years. Three outbreaks affecting 46 patients were spatially spaced, with 11 to 23 persons each. Different groups exhibited varying geographic distances between the initial and later cases. There are areas with a high risk of transmission for M. tuberculosis in the research site, and the risk varies among different populations. Accurate prevention strategies targeted at specific regions and key populations can help curb the prevalence of TB.

Prevalence and Risk Factors of LTBI at Madura Boarding School as a High-Risk Congregate Setting

Highlights: Boarding school is a high-risk location for TB transmission. Therefore, stricter early prevention measures are required. Gender and knowledge level were significantly related to LTBI, but there was no significant relationship between age and nutritional status. Low level of knowledge was the highest risk factor compared to other factors, with a five times greater risk of contracting LTBI. Abstract Introduction: Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a highly contagious airborne disease. High-risk environments with frequent close interactions contribute to the spread of TB. This study examined latent TB infection (LTBI) epidemiology in such settings to inform public health interventions and strategies to curb TB transmission in similar environments. Methods: This cross-sectional observational study, conducted from January to August 2022 at two boarding schools in Bangkalan, involved 100 adolescents aged 10-18 years old tested for LTBI using interferon-gamma (IFN-γ) release assay (IGRA). Data were collected via questionnaires. Bivariate analysis was used to determine the correlation between LTBI prevalence and each research variable using Pearson correlation and odds ratio (OR). A p-value &lt;0.05 was considered statistically significant. Results: This study found that 30% of 100 adolescents in boarding schools had LTBI. Risk analysis showed a significant association between gender and LTBI, with males having a 1.02 times higher risk (p-value 0.000). Additionally, lower education levels were significantly associated with a 5.2 times higher risk of LTBI (p-value 0.021). Conclusion: Boarding schools pose a TB transmission risk. Early LTBI screening is essential for TB eradication in Indonesia, and these findings emphasize the need to improve LTBI detection and prophylaxis therapy as a preventive measure against TB outbreaks.

Phylogenetic analysis of Mycobacterium caprae highlights past and present epidemiological links at the Iberian Peninsula scale

Mycobacterium caprae is linked to regular outbreaks of tuberculosis (TB) in geographically distinct caprine populations across Europe, namely Iberia where this ecovar may represent 8% of total animal TB cases, circulating in multi-host communities encompassing domestic ruminants and wildlife, representing severe financial losses. It also causes zoonotic human disease. In this work, we undertake the first phylodynamic and phylogeographic analyses of M. caprae to reconstruct past demography and transmission chains. First, we examined the worldwide diversity of M. caprae based on 229 unpublished and publicly available whole genome sequences, depicting Asian, Central-East European, and Iberian clades. Phylodynamic analyses of the SB0157 Iberian clade (n=81) positioned the most recent common ancestor in goats, around 100 years ago. Host transition events were common between goats, wild boars, and humans, possibly resulting from mixed farming, extensive management, and close human proximity, facilitating interspecific transmission. We show the spread of M. caprae on multiple scales due to local and transnational animal trade, supporting historical and sustained cross-species transmission in Iberia. We highlight the value of intersecting genomic epidemiology with molecular ecology to resolve epidemiological links and show that an EU-official eradication program in goats is utterly needed to control TB in a multi-host scenario.

Dynamical System for Tuberculosis Outbreak with Vaccination Treatment and Different Interventions on the Burden of Drug Resistance

Tuberculosis, a highly contagious and lethal infectious disease, remains a global health concern with challenging treatment options. To combat its widespread impact, prevention strategies, such as vaccination, are imperative. This research focuses on developing a mathematical model with the addition of a vaccination compartment to understand the dynamics of tuberculosis transmission with vaccination. Subsequently, the study proceeds to identify the equilibrium points and calculate the basic reproduction number (ℜ0). Following this, a comprehensive stability analysis is conducted, and a numerical simulation is executed to observe the population dynamics. Furthermore, parameter sensitivity analysis is undertaken to assess the extent to which these parameters impact ℜ0. Preliminary analysis shows that the modified model has a solution that remains in the non-negative and bounded region. Furthermore, model analysis reveals two equilibrium points, namely the disease-free equilibrium and the endemic equilibrium. It is established that the disease-free equilibrium exhibits local asymptotic stability when ℜ0 1. Remarkably, the numerical simulation aligns with the analytical findings, reinforcing the robustness of the results. Analysis of the sensitivity of the parameter to ℜ0 shows that the parameter of the proportion of susceptible population entering the vaccination class has a significant effect on the value of ℜ0. The parameter of proportion of susceptible population entering the vaccination class has a negative effect on the number of populations with infection.

Associations of community knowledge, perceptions, and practices related to zoonotic disease with sociodemographic factors in and around Chiro Town, Eastern Ethiopia: a cross-sectional study

BackgroundZoonoses are infectious diseases that are transmitted from animals to humans. Studying the knowledge, perceptions and practices of communities related to zoonoses and the associated risk factors is crucial for effective control and prevention. This study aimed to assess the knowledge, perceptions, and practices of respondents on zoonoses and the associated risk factors in and around Chiro town, Ethiopia. Zoonotic diseases, such as rabies, anthrax, bovine tuberculosis, and brucellosis, pose a direct threat to health and livelihoods in the communities where they occur. These diseases emerge due to a combination of human-animal interactions, migration, and contact with wildlife and their respective parasites and vectors. Hence, recognizing residents’ perceptions, knowledge, and practices is crucial for effectively minimizing risks.MethodsA cross-sectional study was conducted from January 2020 to July 2021 in and around Chiro town using a pretested close-ended questionnaire. A total of 350 respondents were selected using simple random sampling methods. The questionnaire included information on the sociodemographic status of the respondents and questions concerning the knowledge, perceptions, and practices of the participants regarding the selected zoonotic diseases. The associations of knowledge, perceptions, and practices related to zoonoses with zoonotic risk factors were analysed using chi-square tests.ResultsThe study revealed that 82.9% of the respondents had knowledge of bovine tuberculosis, followed by knowledge of rabies (80%), knowledge of anthrax (45.1%), and knowledge of brucellosis (24.3%). Males had greater knowledge of bovine tuberculosis (84.8%), followed by rabies (79.8%) and anthrax (48.6%), while females had greater knowledge of brucellosis (23.6%). The most cited source of information was radio (68%). Most respondents mentioned the outbreaks of rabies (62.5%), bovine tuberculosis (53.2%), anthrax (35.6%), and brucellosis (15.7%). Respondents with higher educational levels and urban residents had more knowledge of zoonoses. More than 75% of respondents had a good perception of the transmission of zoonotic disease from animals, and the practice of consuming raw milk or raw/undercooked meat and sharing the same house with animals was high.ConclusionThe majority of respondents reported that they had knowledge of bovine tuberculosis and rabies, but lower knowledge and perceptions were reported for anthrax and brucellosis. These findings illustrate the need for collaboration among animal, human and environmental health offices in one health approach to prevent and control zoonotic disease.

Evaluation of Whole Genome Sequencing-Based Predictions of Antimicrobial Resistance to TB First Line Agents: A Lesson from 5 Years of Data.

Phenotypic susceptibility testing of the Mycobacterium tuberculosis complex (MTBC) isolate requires culture growth, which can delay rapid detection of resistant cases. Whole genome sequencing (WGS) and data analysis pipelines can assist in predicting resistance to antimicrobials used in the treatment of tuberculosis (TB). This study compared phenotypic susceptibility testing results and WGS-based predictions of antimicrobial resistance (AMR) to four first-line antimicrobials-isoniazid, rifampin, ethambutol, and pyrazinamide-for MTBC isolates tested between the years 2018-2022. For this 5-year retrospective analysis, the WGS sensitivity for predicting resistance for isoniazid, rifampin, ethambutol, and pyrazinamide using Mykrobe was 86.7%, 100.0%, 100.0%, and 47.8%, respectively, and the specificity was 99.4%, 99.5%, 98.7%, and 99.9%, respectively. The predictive values improved slightly using Mykrobe corrections applied using TB Profiler, i.e., the WGS sensitivity for isoniazid, rifampin, ethambutol, and pyrazinamide was 92.31%, 100%, 100%, and 57.78%, respectively, and the specificity was 99.63%. 99.45%, 98.93%, and 99.93%, respectively. The utilization of WGS-based testing addresses concerns regarding test turnaround time and enables analysis for MTBC member identification, antimicrobial resistance prediction, detection of mixed cultures, and strain genotyping, all through a single laboratory test. WGS enables rapid resistance detection compared to traditional phenotypic susceptibility testing methods using the WHO TB mutation catalog, providing an insight into lesser-known mutations, which should be added to prediction databases as high-confidence mutations are recognized. The WGS-based methods can support TB elimination efforts in Canada and globally by ensuring the early start of appropriate treatment, rapidly limiting the spread of TB outbreaks.

Genomic insights into anthropozoonotic tuberculosis in captive sun bears (Helarctos malayanus) and an Asiatic black bear (Ursus thibetanus) in Cambodia

Contact between humans and wildlife presents a risk for both zoonotic and anthropozoonotic disease transmission. In this study we report the detection of human strains of Mycobacterium tuberculosis in sun bears and an Asiatic black bear in a wildlife rescue centre in Cambodia, confirming for the first time the susceptibility of these bear species to tuberculosis when in close contact with humans. After genotyping revealed two different strains of M. tuberculosis from cases occurring between 2009 and 2019, 100 isolates from 30 sun bear cases, a single Asiatic black bear case, and a human case were subjected to whole genome sequencing. We combined single nucleotide polymorphism analysis and exploration of mixed base calls with epidemiological data to indicate the evolution of each outbreak. Our results confirmed two concurrent yet separate tuberculosis outbreaks and established a likely transmission route in one outbreak where the human case acted as an intermediatory between bear cases. In both outbreaks, we observed high rates of transmission and progression to active disease, suggesting that sun bears are highly susceptible to tuberculosis if exposed under these conditions. Overall, our findings highlight the risk of bi-directional transmission of tuberculosis between humans and captive bears in high human tuberculosis burden regions, with implied considerations for veterinary and public health. We also demonstrate the use of standard genomic approaches to better understand disease outbreaks in captive wildlife settings and to inform control and prevention measures.

A review of bovine tuberculosis transmission risk in European wildlife communities

Abstract Understanding how disease moves through wildlife communities is essential to managing outbreaks of zoonotic diseases across the globe. Bovine tuberculosis is a disease caused by the bacterium Mycobacterium bovis that can threaten domestic and wildlife species. The mechanism by which Mycobacterium bovis is spread between species is still poorly understood. Previous reviews are limited in the breadth of species considered and are primarily concerned with transmission from wildlife to domestic species. We conducted a review and analysis of Mycobacterium bovis prevalence rates in European wildlife species to identify species of concern for the transmission of bovine tuberculosis in a wildlife community. We subsequently conducted a narrative review of these species assessing the risk of Mycobacterium bovis transmission in a wildlife community based on available literature. We calculated weighted mean disease prevalence rates to be highest in fallow deer (Dama dama, 20%), Eurasian badgers (Meles meles, 11%), wild boar (Sus scrofa, 9%) and red foxes (Vulpes vulpes, 4%). We considered these species to be of particular concern for the transmission of Mycobacterium bovis and selected them as the focus of our narrative review and risk assessment. Our risk assessment considered disease pathology, spatiotemporal activity patterns and animal behaviour as factors affecting the likelihood of Mycobacterium bovis transmission between wildlife species. We found that prior research has principally focused on a few individual species, but that Mycobacterium bovis transmission through a wildlife community is likely more complex. We determined that disease transmission between multiple species may compound the severity of an outbreak of bovine tuberculosis. Broad, multi‐species sampling campaigns and standardised Mycobacterium bovis testing protocols should be implemented in future studies. We also determined that an in‐depth analysis of spatiotemporal overlap between species was needed to better assess the risk of transmission between wildlife species.

Intradermal Tuberculin Test in Water Buffalo (Bubalus bubalis): Experimental use of Mycobacterial Antigens for the Diagnosis of Bovine Tuberculosis

The study aims to evaluate the potential use of mycobacterial ESAT6 and CFP10 antigens, Early Secretory Proteins (ESP) in the Skin Test used for bovine tuberculosis (TB) diagnosis in Water Buffalo.&#x0D; A pilot study was performed on 21 buffaloes from a TB outbreak and 11 buffaloes from a TB-free herd. Three concentrations of ESAT6-CFP10 (10, 20, and 30 mg) and two of ESP (50 and 100 µg) were inoculated in the Skin Test, along with PPDB, PPDA, and PBS as a negative control. Skin thickness was measured with calipers before the test and every 24 hours for 4 days. Then, to evaluate the specificity of the antigens, a field study was conducted, and 100 buffaloes from a TB-free herd were inoculated using the best antigens concentration derived from the pilot study.&#x0D; In the positive buffaloes, the strongest skin response was to PPDB at 24h, with some subjects becoming inconclusive at 72 and 96 h. A peak response to PPDA at 48 hours was detected, followed by a slight decrease. The response to ESP-100 µg remained high at 24 and 48 h, then decreased, remaining positive at 72 h. In the 100 TB-free buffaloes, the best specificity was observed using ESAT6-CFP10 and ESP.&#x0D; ESP yielded the best results, showing higher reactivity in infected animals and no reactivity in the healthy ones at 72 h. Therefore, ESP could be an excellent candidate for further extensive studies in the buffalo species to improve Skin Test performance.

4-(Benzyloxy)phenol-induced p53 exhibits antimycobacterial response triggering phagosome-lysosome fusion through ROS-dependent intracellular Ca2+ pathway in THP-1 cells

Drug-resistant tuberculosis (TB) outbreak has emerged as a global public health crisis. Therefore, new and innovative therapeutic options like host-directed therapies (HDTs) through novel modulators are urgently required to overcome the challenges associated with TB. In the present study, we have investigated the anti-mycobacterial effect of 4-(Benzyloxy)phenol. Cell-viability assay asserted that 50 μM of 4-(Benzyloxy)phenol was not cytotoxic to phorbol 12-myristate 13-acetate (PMA) differentiated THP-1 (dTHP-1) cells. It was observed that 4-(Benzyloxy)phenol activates p53 expression by hindering its association with KDM1A. Increased ROS, intracellular Ca2+ and phagosome-lysosome fusion, were also observed upon 4-(Benzyloxy)phenol treatment. 4-(Benzyloxy)phenol mediated killing of intracellular mycobacteria was abrogated in the presence of specific inhibitors of ROS, Ca2+ and phagosome-lysosome fusion like NAC, BAPTA-AM, and W7, respectively. We further demonstrate that 4-(Benzyloxy)phenol mediated enhanced ROS production is mediated by acetylation of p53. Blocking of p53 acetylation by Pifithrin-α (PFT- α) enhanced intracellular mycobacterial growth by blocking the mycobactericidal effect of 4-(Benzyloxy)phenol. Altogether, the results showed that 4-(Benzyloxy)phenol executed its anti-mycobacterial effect by modulating p53-mediated ROS production to regulate phagosome-lysosome fusion through Ca2+ production.

Outbreak of Mycobacterium orygis in a Shipment of Cynomolgus Macaques Imported from Southeast Asia - United States, February-May 2023.

Nonhuman primates (NHP) can become infected with the same species of Mycobacteria that cause human tuberculosis. All NHP imported into the United States are quarantined and screened for tuberculosis; no confirmed cases of tuberculosis were diagnosed among NHP during CDC-mandated quarantine during 2013-2020. In February 2023, an outbreak of tuberculosis caused by Mycobacterium orygis was detected in a group of 540 cynomolgus macaques (Macaca fascicularis) imported to the United States from Southeast Asia for research purposes. Although the initial exposure to M. orygis is believed to have occurred before the macaques arrived in the United States, infected macaques were first detected during CDC-mandated quarantine. CDC collaborated with the importer and U.S. Department of Agriculture's National Veterinary Services Laboratories in the investigation and public health response. A total of 26 macaques received positive test results for M. orygis by culture, but rigorous occupational safety protocols implemented during transport and at the quarantine facility prevented cases among caretakers in the United States. Although the zoonotic disease risk to the general population remains low, this outbreak underscores the importance of CDC's regulatory oversight of NHP importation and adherence to established biosafety protocols to protect the health of the United States research animal population and the persons who interact with them.

On the onset and dispersal of a major MDR TB clone among HIV-negative patients, Tunisia

BackgroundTo carry out a whole genome sequencing (WGS)-based investigation on the emergence and spread of the largest multidrug-resistant tuberculosis (MDR TB) outbreak that has been thriving among HIV-negative patients, Tunisia, since the early 2000s.MethodsWe performed phylogeographic analyses and molecular dating based on a WGS dataset representing 68 unique Mycobacterium tuberculosis isolates, covering almost the entire MDR TB outbreak for the time period 2001–2016.ResultsThe data indicate that the ancestor of the MDR TB outbreak emerged in the region of Bizerte, as early as 1974 (95% CI 1951–1985), from where it spread to other regions by 1992 (95% CI 1980–1996). Analysis of a minimum spanning tree based on core genome Multilocus Sequence Typing (cgMLST) uncovered the early spill-over of the fitness-compensated MDR TB strain from the prison into the general population. Indeed, cases with history of incarceration were found to be directly or indirectly linked to up to 22 new outbreak cases (32.35%) among the non-imprisoned population. By around 2008, the MDR TB outbreak strain had acquired additional resistance, leading to an XDR phenotype.ConclusionsWGS allowed refining our understanding of the emergence and evolution of the largest MDR TB outbreak in Tunisia, whose causative strain has been circulating silently for almost 26 years before. Our study lends further support to the critical role of prisons-related cases in the early spread of the outbreak among the general population. The shift to an XDR phenotype of such an epidemic clone prompts an urgent need to undertake drastic control measures.

Metabolites from Streptomyces aureus (VTCC43181) and Their Inhibition of Mycobacterium tuberculosis ClpC1 Protein.

Tuberculosis is one of the most common infectious diseases in the world, caused by Mycobacterium tuberculosis. The outbreak of multiple drug-resistant tuberculosis has become a major challenge to prevent this disease worldwide. ClpC1 is a Clp ATPase protein of Mycobacterium tuberculosis, functioning as a chaperon when combined with the Clp complex. ClpC1 has emerged as a new target to discover anti-tuberculosis drugs. This study aimed to explore the ClpC1 inhibitors from actinomycetes, which have been known to provide abundant sources of antibiotics. Two cyclic peptides, including nocardamin (1), halolitoralin A (3), and a lactone pleurone (2), were isolated from the culture of Streptomyces aureus (VTCC43181). The structures of these compounds were determined based on the detailed analysis of their spectral data and comparison with references. This is the first time these compounds have been isolated from S. aureus. Compounds 1-3 were evaluated for their affection of ATPase activity of the recombinant ClpC1 protein. Of these compounds, halolitoralin A (1), a macrocyclic peptide, was effective for the ATPase hydrolysis of the ClpC1 protein.

The Challenges of Tuberculosis Management beyond Professional Competence: Insights from Tuberculosis Outbreaks among Ethiopian Immigrants in Israel.

Controlling tuberculosis (TB) among immigrants from high-incidence countries presents a public health concern as well as a medical challenge. In this article, we investigate a TB outbreak in a community of people of Jewish descent who emigrated from Ethiopia to Israel (Israeli Ethiopians) that started in June 2022. The index case was a 20-year-old female who had recently immigrated to Israel with her family. Her pre-immigration tuberculin skin test was positive. After excluding active TB, treatment with daily isoniazid for latent TB (LTB) was started shortly after her arrival. A year later, she was diagnosed with smear-positive, culture-positive, pulmonary TB. Investigation of 83 contacts revealed five additional patients with active TB, and three of whom were members were of her household. In this article, we report the current TB outbreak, review previously published TB outbreaks involving Israeli Ethiopians, analyze the factors that triggered each of these outbreaks, and discuss the challenges that face the Israeli TB control program in an era of declining TB incidence and diminishing resources available for TB control.

A humoral diagnostic test outperforms cellular tests in a farm with a latent tuberculosis outbreak caused by a new Mycobacterium tuberculosis complex spoligotype that affected sheep but not goats.

Tuberculosis (TB) is a disease caused by members of the M. tuberculosis complex (MTC) that affects numerous species. M. caprae, a member of the complex which is close to M. bovis, is emerging and affects several different hosts that include goats, cattle, sheep, pigs, rabbits, wild boar, red deer, foxes and also humans. A new M. caprae spoligotype (SB2737) was isolated from an outbreak of sheep tuberculosis affecting a mixed sheep (323)-goat (29) farm in 2021. The index case was detected by the La Rioja slaughterhouse veterinary inspection. Tracing back to the farm of origin, both species were submitted to Comparative Intradermal Tuberculin Test (CITT) and M. bovis-specific antibody ELISA tests. A subsample was also examined by IFN-γ release assay (IGRA) and all positives were slaughtered and pathologically and microbiologically investigated. Only 1.2% of sheep and no goat were positive in the CITT, and 11.4% in the IGRA sheep subsample, while up to 36.8% were positive in two consecutive M. bovis-specific antibody ELISA tests. Goats had always tested negative in annual intradermal follow-up since 2013. Upon confirmation of the immunologically positive sheep at slaughter, all the remaining negative animals were killed and 29.2% of sheep were still found infected. This raised the final overall prevalence to 37.5%. Antibody ELISA was the most sensitive (81.4%) in vivo detection method still showing a 85.0% specificity relative to pathological and microbiological tuberculosis status. It was nearly 10 times more sensitive than skin test and had an 86.8% positive predictive value. Notwithstanding a possible singular pathogenesis of the new spoligotype, this outbreak adds up to previous reports suggesting that sheep tuberculosis could be huge reservoir of infection worldwide overlooked by skin test low sensitivity or simply lack of investigation. This makes it urgent to extend the use antibody tests to address the Trojan horse of hidden M. tuberculosis complex infections on bovine TB control programs.

Socioeconomic impacts of airborne and droplet-borne infectious diseases on industries: a systematic review

BackgroundRecent pandemics have had far-reaching effects on the world’s largest economies and amplified the need to estimate the full extent and range of socioeconomic impacts of infectious diseases outbreaks on multi-sectoral industries. This systematic review aims to evaluate the socioeconomic impacts of airborne and droplet-borne infectious diseases outbreaks on industries.MethodsA structured, systematic review was performed according to the PRISMA guidelines. Databases of PubMed, Scopus, Web of Science, IDEAS/REPEC, OSHLINE, HSELINE, and NIOSHTIC-2 were reviewed. Study quality appraisal was performed using the Table of Evidence Levels from Cincinnati Children’s Hospital Medical Center, Joanna Briggs Institute tools, Mixed Methods Appraisal Tool, and Center of Evidence Based Management case study critical appraisal checklist. Quantitative analysis was not attempted due to the heterogeneity of included studies. A qualitative synthesis of primary studies examining socioeconomic impact of airborne and droplet-borne infectious diseases outbreaks in any industry was performed and a framework based on empirical findings was conceptualized.ResultsA total of 55 studies conducted from 1984 to 2021 were included, reporting on 46,813,038 participants working in multiple industries across the globe. The quality of articles were good. On the whole, direct socioeconomic impacts of Coronavirus Disease 2019, influenza, influenza A (H1N1), Severe Acute Respiratory Syndrome, tuberculosis and norovirus outbreaks include increased morbidity, mortality, and health costs. This had then led to indirect impacts including social impacts such as employment crises and reduced workforce size as well as economic impacts such as demand shock, supply chain disruptions, increased supply and production cost, service and business disruptions, and financial and Gross Domestic Product loss, attributable to productivity losses from illnesses as well as national policy responses to contain the diseases.ConclusionsEvidence suggests that airborne and droplet-borne infectious diseases have inflicted severe socioeconomic costs on regional and global industries. Further research is needed to better understand their long-term socioeconomic impacts to support improved industry preparedness and response capacity for outbreaks. Public and private stakeholders at local, national, and international levels must join forces to ensure informed systems and sector-specific cost-sharing strategies for optimal global health and economic security.

Diagnostic performance of a novel ESAT6-CFP10 skin test for tuberculosis infection in school tuberculosis outbreak in China.

The ESAT6-CFP10 (EC) skin test is recommended by the World Health Organization for latent tuberculosis infection (LTBI). However, it is still unknown how the EC skin test performs in students during a school tuberculosis outbreak. We conducted an epidemiological investigation to assess the performance of the EC skin test in this high-risk population. A total of 9 active student patients were confirmed in the same class as the index case, with an incidence rate of 18.0% (9/50). Among the 50 close contacts, 14 (28%) were over 15 years old and had a chest X-ray (CXR), and none of them had abnormal CXR findings. The rates of positive tuberculin skin test (TST) ≥ 5 mm and < 10 mm, ≥ 10 mm and < 15 mm, and ≥ 15 mm were 12.0% (6/50), 16.0% (8/50), and 10.0% (5/50), respectively. On the second screening, 44 students with the same class as the index case had the EC skin test, of which 31 (70.5%) had positive EC tests. All patients had negative sputum smear results, of whom 4 (44.4%) had positive Xpert results; three had a TST induration diameter between 5 mm and 10 mm, but all of them had an EC diameter > 15 mm; 5 (55.6%) had abnormal CXR results, but all the confirmed patients had abnormal CT results; Except for four cases that were diagnosed by Xpert, the remaining five were confirmed by CT scan. The novel EC skin test performed well in students during the school tuberculosis outbreak. In some special conditions, such as when the index case is bacteriologically positive for tuberculosis and the rate of LTBI is higher than the average for the local same-age group, secondary screening is recommended 2-3 months after the first screening. Furthermore, we cannot ignore the role of CT in the diagnosis of early student tuberculosis.

Novel and reported compensatory mutations in rpoABC genes found in drug resistant tuberculosis outbreaks.

Rifampicin (RIF) is a key first-line drug used to treat tuberculosis, a primarily pulmonary disease caused by Mycobacterium tuberculosis. RIF resistance is caused by mutations in rpoB, at the cost of slower growth and reduced transcription efficiency. Antibiotic resistance to RIF is prevalent despite this fitness cost. Compensatory mutations in rpoABC genes have been shown to alleviate the fitness cost of rpoB:S450L, explaining how RIF resistant strains harbor this mutation can spread so rapidly. Unfortunately, the full set of RIF compensatory mutations is still unknown, particularly those compensating for rarer RIF resistance mutations. We performed an association study on a globally representative set of 4,309 whole genome sequenced clinical M. tuberculosis isolates to identify novel putative compensatory mutations, determine the prevalence of known and previously reported putative compensatory mutations, and determine which RIF resistance markers associate with these compensatory mutations. Of the 1,079 RIF resistant isolates, 638 carried previously reported putative and high-probability compensatory mutations. Our strict criteria identified 46 additional mutations in rpoABC for which no strong prior evidence of their compensatory role exists. Of these, 35 have previously been reported. As such, our independent corroboration adds to the mounting evidence that these 35 also carry a compensatory role. The remaining 11 are novel putative compensatory markers, reported here for the first time. Six of these 11 novel putative compensatory mutations had two or more mutation events. Most compensatory mutations appear to be specifically compensating for the fitness loss due to rpoB:S450L. However, an outbreak of 22 closely related isolates each carried three rpoB mutations, the rare RIFR markers D435G and L452P and the putative compensatory mutation I1106T. This suggests compensation may require specific combinations of rpoABC mutations. Here, we report only mutations that met our very strict criteria. It is highly likely that many additional rpoABC mutations compensate for rare resistance-causing mutations and therefore did not carry the statistical power to be reported here. These findings aid in the identification of RIF resistant M. tuberculosis strains with restored fitness, which pose a greater risk of causing resistant outbreaks.