Endemic Tuberculosis Research Articles

P016 IMPROVING TUBERCULOSIS RE SCREENING IN INFLAMMATORY BOWEL DISEASE PATIENTS RECEIVING BIOLOGIC THERAPY: A SINGLE CENTER QUALITY IMPROVEMENT INITIATIVE.

Abstract Background Biological agents have revolutionized the management of inflammatory bowel disease (IBD). There is a known increased risk of tuberculosis (TB) reactivation with biologic therapy (1). ACG guidelines recommend screening for active and latent TB infection (LTBI) prior to starting certain biologic agents (2). However, there are no consensus guideline on the utility of yearly screening testing in IBD patients without TB risk factors. With a number of patients now receiving the biologic therapy outside their primary care centers it has become increasingly difficult to effectively provide ongoing TB screening. With this quality improvement exercise, we aim to improve TB re-screening in patients receiving biologics by completing a yearly phone screening for exposure history. Method An interdisciplinary team from GI and ID developed a TB risk factor screening questionairre, adapting the California Department of Public Health’s Pediatric TB Risk Assessment tool (3). A list of patients receiving biologics was sorted by month of birth in the EMR. When the current calendar month aligned with the patient’s birth month, a GI RN reviewed the TB questionnaire with the patient (≥18 yo) and/or legal guardian by phone. If one or more TB risk factors were identified, the GI RN would notify the provider and a QuantiFERON-TB Gold (QFT) was ordered to be completed. Results 60 patients were found on biologic therapy (median age 17 yo) (38 males, 22 females) (68% CD, 28% UC, 3.3% IBD-U)(75% IFX, 12% ADA, and 3% other) to be to eligible TB screening between January - July 2019, 48 patients completed the phone screening. All 61 patients had completed TB screening prior to starting biologic therapy, which was reported to be negative. 13 patients were unable to be reached. 6/48 were identified as having at least 1 risk factor for TB. 5/6 patients with a positive screen had a negative QFT. 1 patient was away at college and a request to his adult GI managing his biologic was sent. Conclusion Screening for LTBI is required prior to starting a biologic therapy, though there are no guidelines for routine TB screening following initiation of the biologic. We propose performing an annual phone screening for TB exposure history for IBD patients on biologic therapy. QTF testing remains appropriate in patients with potential risk factors, such as being a health care worker or travel to/living in high endemic TB regions. References

Case report: association between lymph node tuberculosis and breast cancer

Introduction: Lymph node tuberculosis is the most common extra-lung presentation of tuberculosis, responsible for 43% of peripheral lymphadenopathies in developing countries. The coexistence between lymph node tuberculosis and breast cancer is rare, ranging from 0.1% to 4.9%.Objective: To present a case of axillary lymph node tuberculosis due to its rare association with breast cancer. Methods: We have investigated the case of a 48-year-old woman from Congonhas, Minas Gerais, Southeastern Brazil, who presented a palpable nodule in the junction of the right upper quadrants with two years of progression, category 4B of the Breast Imaging Reporting and Data System (BI-RADS) on mammography and ultrasound, with core needle biopsy compatible with benignancy. No axillary lymphadenopathy was identified. Case report: The patient underwent resection of the right breast nodule with safety margins due to disagreement between biopsy and imaging tests. Anatomopathological examination was consistent with luminal B invasive ductal carcinoma, measuring 1.6 cm. The patient was submitted to sentinel lymph node biopsy using patent blue in the right axilla. Anatomopathological analysis revealed tuberculous lymphadenitis. Chest computed tomography showed pulmonary nodules. The patient received adjuvant radiotherapy and tamoxifen, as well as antituberculous antibiotics, with regression of pulmonary nodules. The final staging was pT1cN0M0- IA. Discussion: Most cases of coexistence between these diseases involve tuberculous lymphadenitis with or without neoplastic lymph node involvement. Some reports indicate that the involvement by tuberculosis does not prevent neoplastic proliferation. Before starting chemotherapy, tuberculosis must be treated to avoid the immunosuppressive effect that can cause a spread of tuberculosis. Conclusion: Despite the rare coexistence of these diseases, we should not rule out this possibility, especially in endemic tuberculosis areas. Also, an accurate diagnosis prevents incorrect staging and can spare the patient from a more aggressive treatment.

Analysis of the development of tuberculosis as an epidemic process in the student environment of the Оrenburg region

The analysis of epidemic situation on tuberculosis, features of detection of disease, and also clinical and epidemiological characteristics for the first time revealed specific process in separate social group of students of the special and higher educational organizations of the Orenburg region for 2000–2018 was carried out. ­Me­thods. The indicators of incidence of tuberculosis of respiratory organs and extra-thoracic localization, indicators of morbidity with established bacterial excretion, indicators of morbidity in the presence of pulmonary tissue decay, indicators of the ratio of patients from secondary or higher educational institutions were calculated. The number of students in the region has undergone signi­ficant changes in recent decades. Since 2000, there has been a tendency for its growth with a maximum value in 2009. Subsequently, there was an annual decrease in the number of students, mainly at the expense of higher education institutions. Were identified different periods in endemic tuberculosis region's population, and the dynamics of tuberculosis morbidity students were subject to fluctuations, but generally consistent with such, the total population of the region. It was revealed that focal and infiltrative pulmonary tuberculosis remained the dominant clinical forms for nineteen years. The absence in the clinical structure of respiratory tuberculosis in students of classical forms of primary tuberculosis (tuberculosis of the intrathoracic lymph nodes, primary tuberculosis complex) confirms the completed early period of primary tuberculosis infection, that is, the previous infection of students with Mycobacterium tuberculosis. The obtained results indicate the endogenous reactivation of tuberculosis infection as a priority pathogenesis of the disease in this population group. Among the students of the region in recent years, there has been a tendency to reduce the incidence of tuberculosis. The structure of morbidity is dominated by small uncomplicated forms of tuberculosis of the respiratory system, identified during preventive examinations. Conclusion. In General, over the past de­cades in the Orenburg region there is a tense epidemic situation in the incidence of tuberculosis of students with a characteristic tendency to improve it.

Decision tree machine learning applied to bovine tuberculosis risk factors to aid disease control decision making

Identifying and understanding the risk factors for endemic bovine tuberculosis (TB) in cattle herds is critical for the control of this disease. Exploratory machine learning techniques can uncover complex non-linear relationships and interactions within disease causation webs, and enhance our knowledge of TB risk factors and how they are interrelated. Classification tree analysis was used to reveal associations between predictors of TB in England and each of the three surveillance risk areas (High Risk, Edge, and Low Risk) in 2016, identifying the highest risk herds. The main classifying predictor for farms in England overall related to the TB prevalence in the 100 nearest cattle herds. In the High Risk and Edge areas it was the number of slaughterhouse destinations and in the Low Risk area it was the number of cattle tested in surveillance tests. How long ago the last confirmed incident was resolved was the most frequent classifier in trees; if within two years, leading to the highest risk group of herds in the High Risk and Low Risk areas. At least two different slaughterhouse destinations led to the highest risk group of herds in England, whereas in the Edge area it was a combination of no contiguous low-risk neighbours (i.e. in a 1 km radius) and a minimum proportion of 6–23 month-old cattle in November. A threshold value of prevalence in 100 nearest neighbours increased the risk in all areas, although the value was specific to each area. Having low-risk contiguous neighbours reduced the risk in the Edge and High Risk areas, whereas high-risk ones increased the risk in England overall and in the Edge area specifically. The best classification tree models informed multivariable binomial logistic regression models in each area, adding statistical inference outputs. These two approaches showed similar predictive performance although there were some disparities regarding what constituted high-risk predictors. Decision tree machine learning approaches can identify risk factors from webs of causation: information which may then be used to inform decision making for disease control purposes.

Histoplasmosis and Tuberculosis Co-Occurrence in People with Advanced HIV.

Distinguishing between histoplasmosis, tuberculosis (TB), and co-occurrence of disease is a frequent dilemma for clinical staff treating people with advanced Human Immunodeficiency Virus (HIV) infection. This problem is most frequently observed in clinical settings in countries where both diseases are endemic. It is also a challenge outside these endemic countries in HIV clinics that take care of patients coming from countries with endemic histoplasmosis and TB. The gold standard for diagnosis of both of these diseases is based on conventional laboratory tests (culture, histopathology and special stains). These tests have several limitations, such as lack of laboratory infrastructure for handling isolates (biosafety level 3), shortage of laboratory staff who have appropriate training and experience, variable analytical performance of tests and long turn-around time. Recently, novel rapid assays for the diagnosis of histoplasmosis and TB became available. However, this technology is not yet widely used. Mortality in immunocompromised patients, such as people with advanced HIV, is directly linked with the ability to rapidly diagnose opportunistic diseases. The aim of this review is to synthesize the main aspects of epidemiology, clinical characteristics, diagnosis and treatment of histoplasmosis/TB co-occurrence in people with advanced HIV.

Minipigs as a neonatal animal model for tuberculosis vaccine efficacy testing

Many vaccines against childhood diseases are administered early after birth, but vaccine development studies frequently test efficacy in adult rather than in neonatal animal models. In countries with endemic tuberculosis (TB), Bacillus Calmette-Guerin (BCG) is administered as part of the neonatal vaccine regimen because it prevents against the disseminated form of TB in children, although it has variable efficacy against pulmonary TB. Several promising new vaccines against TB are currently being tested in adult animal models. Here we evaluated neonatal piglets as an animal model to test vaccine efficacy. For this purpose, minipigs were vaccinated or not with BCG 48 h after birth and their immune response followed longitudinally until adolescence. We characterized the memory and activation phenotype of T cells, cytokine profile, and monocyte activation in response to BCG stimulation from 4 weeks of age into adolescence- age of 24 weeks. Immunological responses in vaccinated and non-vaccinated animals were further monitored upon infection with a low dose exposure to Mycobacterium tuberculosis strain HN878 via the aerosol route. Comparing the immunological response elicited by BCG vaccination in minipigs vs similar studies in infants, suggest that minipigs have the potential to serve as an effective neonatal animal model for vaccine development.

Impact of HIV on spontaneous spondylodiscitis.

HIV predisposes patients to opportunistic infections. However, with the establishment of Highly Active Anti-Retroviral Therapy (HAART), patients' CD4 counts are maintained, as is a near normal life expectancy. This study aimed to establish the impact of HIV on the bacteriology of spondylodiscitis in a region in which tuberculosis (TB) is endemic, and to identify factors that might distinguish between them. Between January 2014 and December 2015, 63 consecutive cases of spontaneous spondylodiscitis were identified from a single-centre, prospectively maintained database. Demographics, presenting symptoms, blood results, HIV status, bacteriology, imaging, and procedure undertaken were reviewed and comparisons made of TB, non-TB, and HIV groups. There were 63 patients (22 male, 41 female) with a mean age of 42.0 years (11 to 78; sd 15.0). In total, 53 patients had tuberculous, nine bacterial, and one cryptococcal spondylodiscitis. There were 29 HIV-positive patients, 29 HIV-negative patients, and five patients with unknown HIV status. The local incidence of TB spondylodiscitis was 1.54/100 000 and that of non-TB spondylodiscitis was 0.29/100 000 per annum. TB patients were younger with similar clinical presentation and infective markers, but were more likely to have a paraspinal abscess. They were also less likely to have a hyperintense disc on MRI. There was no difference between the two HIV groups. In areas of endemic TB and HIV, TB remains the most common cause of spondylodiscitis at five times the rate of non-tuberculous causes. HIV managed with HAART increases the rate of infection but does not influence the bacteriology unless there is a low CD4. There was little to differentiate the groups. TB /HIV co-infected patients were younger than non-TB and HIV-negative patients. Non-TB patients were more likely to have disc hyperintensity on MRI and TB patients were more likely to have abscess formation, but as both groups exhibited these features, neither was diagnostic. Culture confirmation remains necessary. Cite this article: Bone Joint J 2019;101-B:617-620.

Sequencing of the entire rpob gene and characterization of mutations in isolates of Mycobacterium tuberculosis circulating in an endemic tuberculosis setting.

To evaluate the use of a sequencing procedure for the entire rpoB gene of Mycobacterium tuberculosis to identify mutations pre-rifampicin resistance determining region (RRDR), within RRDR, and post-RRDR in isolates circulating in a region affected by tuberculosis (TB). Five primers were designed, with which five DNA fragments of rpoB were obtained, sequenced by Sanger, and analysed in silico in order to identify mutations over the entire rpoB gene in rifampicin-sensitive and rifampicin-resistant TB. It was possible to analyse the entire rpoB gene in five rifampicin-sensitive and 15 rifampicin-resistant isolates. Thirty-six mutations were identified. Two mutations were found pre-RRDR, nine within-RRDR and 25 post-RRDR. The most frequent mutations within RRDR were S531L (53%), followed by S512T (20%), all of which were found in rifampicin-resistant isolates. Of the 25 mutations found post-RRDR, 14 were only in resistant isolates, and the most frequent was D853N, which was present in 85% of isolates. Mutations E818K, D836N and T882P were observed in 80% of the rifampicin-resistant and rifampicin-sensitive isolates. The proposed sequencing method allowed identification of mutations in the entire rpoB gene. This procedure represents a useful tool for diagnosing rifampicin resistance. The number of mutations that were found raises new questions about the diversity of mutations in the rpoB gene and their role in rifampicin resistance in regions where TB is endemic.

Pneumonectomy for non-tumoral diseases: etiologies and follow-up in 38 cases.

Pneumonectomy is a surgical procedure associated with high rates of morbidity and mortality. Chronic inflammatory pathologies increase these rates, depending on the degree of pleural symphysis and the underlying pulmonary pathology. The occurrence of a bronchopleural fistula after pneumonectomy remains of great concern to the thoracic surgeon, because it leads to empyema in the pneumonectomy cavity, which requires protracted and difficult management. A retrospective single-center study was carried out on 38 patients who underwent pneumonectomy for non-tumoral pathologies between 2010 and 2017. Of the 38 patients, 22 (57.8%) men and 16 (42.2%) women, the average age was 40.3 years, and 30 (79%) patients were treated for tuberculosis. The symptoms were predominantly hemoptysis with bronchorrhea in 22 (57.9%) cases. Chest computed tomography showed right-sided involvement in 15 (39.5%) patients, with destroyed lung in 31 (81.5%). Early postoperative complications included bleeding in 11 (28.9%) patients, postpneumonectomy empyema in 4 (10.5%), and death in 2 (5.2%). The average duration of follow-up was 2 years, without any recurrence. The endemicity of tuberculosis in our context, and the absence of screening for lung cancer, explain the frequency of pneumonectomy for chronic inflammatory diseases, and the rate of complications after this surgical procedure.

Mycobacterium caprae Infection of Red Deer in Western Austria-Optimized Use of Pathology Data to Infer Infection Dynamics.

Austria is officially bovine tuberculosis (TB) free, but during the last decade the west of the country experienced sporadic TB cases in cattle. Free-ranging red deer are known to be the maintenance host of Mycobacterium (M.) caprae in certain areas in Austria, where cattle can become infected on alpine pastures shared with deer. The epidemiology of TB in deer in alpine regions is still poorly understood. To inform decisions on efficient interventions against TB in deer, a method is needed to better capture the infection dynamics on population level. A total of 4,521 free-ranging red deer from Austria's most western Federal state Vorarlberg were TB-tested between 2009 and 2018. M. caprae was confirmed in samples from 257 animals. Based on descriptions of TB-like lesions, TB positive animals were categorized with a newly developed lesion score called “Patho Score.” Analyses using this Patho Score allowed us to distinguish between endemic, epidemic and sporadic TB situations and revealed different roles of subgroups of infected deer in infection dynamics. Overall, deer in poor condition, deer of older age and stags were the subgroups that were significantly more often TB positive (p = 0.02 or smaller for all subgroups). Deer in poor condition (p < 0.001) and stags (p = 0.04) also showed more often advanced lesions, indicating their role in mycobacterial spread. TB was never detected in fawns, while hinds were the subgroup that showed the fewest advanced lesions. Analysis of outbreaks of TB and lesion development in yearlings provided some evidence for the role of winter feeding as a source for increased infection transmission. Sporadic cases in TB-free areas appear to precede outbreaks in these areas. These currently TB-free areas should receive particular attention in sampling schemes to be able to detect early spreading of the infection. The Patho Score is a quick, easy-to-apply and reproducible tool that provides new insights on the epidemiology of TB in deer at population level and is flexible enough to relate heterogeneous wildlife monitoring data collected following different sampling plans. This lesion score was used for systematic assessment of infection dynamics of mycobacterial infections.

Faulty kinase purged by tuberculosis?

Tuberculosis Rare mutations in genes involved in interferon-γ–dependent immunity underpin human genetic susceptibility to severe mycobacterial diseases, including primary tuberculosis. Boisson-Dupuis et al. investigated whether two common missense variants of the TYK2 Janus kinase that have impaired catalytic activity conferred an increased risk of tuberculosis. Individuals homozygous for the P1104A (proline to alanine substitution at residue 1104) variant of TYK2 are markedly predisposed to developing primary tuberculosis, defining a common monogenic etiology for the “white plague.” The current frequency of the P1104A allele in European populations is significantly decreased compared with its frequency in ancient European DNA samples. These findings suggest that negative selection against the TYK2 P1104A allele by endemic tuberculosis in Europe may have contributed to a slow genetic purge of this susceptibility allele during recent millennia. Sci. Immunol. 3 , eaau8714 (2018).

Tuberculosis and impaired IL-23-dependent IFN-γ immunity in humans homozygous for a common TYK2 missense variant.

Inherited IL-12Rβ1 and TYK2 deficiencies impair both IL-12- and IL-23-dependent IFN-γ immunity and are rare monogenic causes of tuberculosis, each found in less than 1/600,000 individuals. We show that homozygosity for the common TYK2 P1104A allele, which is found in about 1/600 Europeans and between 1/1000 and 1/10,000 individuals in regions other than East Asia, is more frequent in a cohort of patients with tuberculosis from endemic areas than in ethnicity-adjusted controls (P = 8.37 × 10-8; odds ratio, 89.31; 95% CI, 14.7 to 1725). Moreover, the frequency of P1104A in Europeans has decreased, from about 9% to 4.2%, over the past 4000 years, consistent with purging of this variant by endemic tuberculosis. Surprisingly, we also show that TYK2 P1104A impairs cellular responses to IL-23, but not to IFN-α, IL-10, or even IL-12, which, like IL-23, induces IFN-γ via activation of TYK2 and JAK2. Moreover, TYK2 P1104A is properly docked on cytokine receptors and can be phosphorylated by the proximal JAK, but lacks catalytic activity. Last, we show that the catalytic activity of TYK2 is essential for IL-23, but not IL-12, responses in cells expressing wild-type JAK2. In contrast, the catalytic activity of JAK2 is redundant for both IL-12 and IL-23 responses, because the catalytically inactive P1057A JAK2, which is also docked and phosphorylated, rescues signaling in cells expressing wild-type TYK2. In conclusion, homozygosity for the catalytically inactive P1104A missense variant of TYK2 selectively disrupts the induction of IFN-γ by IL-23 and is a common monogenic etiology of tuberculosis.

Risk factors associated with childhood tuberculosis: a case control study in endemic tuberculosis area

Background: Tuberculosis (TB) in childreen is still considered as important public health problems in various countries, including Indonesia. Risk factors related to childhood tuberculosis is crucial to identify in order to conduct prevention effort effectively. The purpose of this research is to determine the effect of environmental health in house, contact history and nutritional status toward childhood tuberculosis.Methods: This research is an analytical observational study using case-control design, with 35 samples of the case and 35 samples of the control. Several variables such as house environment, contact history and nutritional status were obtained by questionnaire and observation in house of respondents. Data analysis was conducted using Logistic Regression test to determine correlation between independent and dependent variables.Results: This research highlighted that contact history and nutritional status were correlated with childhood tuberculosis. While house environment variables such as lighting level, floor type, house occupancy density were not related to the incidence of tuberculosis in children.Conclusions: Contact history and nutritional status were the factors which determined childhood tuberculosis in Banyumas. It is important for parents to maintain good nutritional status of their children and to avoid them from contact with tuberculosis patients.

Diagnostic accuracy of combinations of serological biomarkers for identifying clinical tuberculosis.

Confirmation of tuberculosis (TB) cases in endemic TB settings is a challenge; obtaining fast and cheap, though accurate, diagnostic tools such as biomarkers is thus urgently needed to enable the early detection of TB. This paper evaluates the diagnostic accuracy of combinations of host serological biomarkers for identifying TB. Enzyme-linked immunosorbent assays (ELISA) were used on 70 Venezuelan Creole individuals for evaluating host biomarkers (i.e. CXCL9, sCD14, MMP9 and uPAR proteins) and anti-synthetic peptides covering certain Mycobacterium tuberculosis (Mtb) ESAT-6 (P-12033, P-12034 and P-12037) and Ag85A (P-29878) antigen sequences. The target population consisted of adults having active TB (ATB, n = 28), the tuberculin skin test positive (TST+) or individuals with latent TB infection (LTB, n = 28) and TST- or control subjects (CTRL, n = 14). Receiver operator curve (ROC) analysis revealed good biosignature discriminative ability for 5 serological biomarkers; the accuracy of 3 combinations had a good discriminative ability for diagnosing TB. Anti-P-12034/uPAR detected TB with 96.7% sensitivity and 86.0% specificity, followed by anti-P-12033/uPAR having 96.7% sensitivity and 81.4% specificity. Anti-P-29878/MMP9 had the highest sensitivity (100%), but low specificity (52.17%). Biomarker combinations did not prove efficacious for identifying incipient subclinical TST+TB- subjects at high-risk for TB. The anti-P-12034/uPAR combination could be useful for identifying clinical TB patients. Such an approach holds promise for further validation.

Tuberculose oculaire

Despite extensive investigations, including the use of Interferon-gamma release assays (IGRA), the diagnosis of intraocular tuberculosis (TB) remains challenging. Ocular evidence of Mycobacterium tuberculosis in low endemic countries for TB is extremely rare, leading mostly to a TB-related ocular inflammation presumptive diagnosis. This present work aims: to highlights the main clinical patterns suggestive of ocular TB; and the latest recommended guidelines for diagnosing ocular TB to clarify interferon-gamma release assay (IGRA) contribution and accuracy to the management of intraocular TB and its diagnosis, in addition to other available diagnostic tools, such as tuberculin skin test, bacteriologic and histologic analysis from intra/extra ocular sample and radiographic investigations; to define the accuracy of these diagnostic tools according to the endemic TB prevalence; and finally to identify therapeutic strategies adapted to the main clinical presentations of ocular TB. Our review of the literature shows that management of suspected ocular TB differs significantly based on whether patients are from high or low TB prevalence countries since accuracy of chest X-ray, tuberculin skin test and IGRA is significantly different. Taking into account these discrepancies, distinct guidelines should be determined for managing patients with suspected ocular TB, taking into consideration home prevalence of TB-patients.

Co-management of tuberculosis and diabetes: an integrative reviewManejo integrado de la tuberculosis y la diabetes: revisión integrativa

RESUMOObjetivo.Identificar as evidências sobre manejo integrado de tuberculose e diabetes disponíveis na literatura para o contexto latino-americano.Métodos.Foi realizada uma revisão integrativa da literatura com busca nas bases de dados LILACS, Web of Science e PubMed. A estratégia utilizou como termos de busca “tuberculose”, “diabetes mellitus” e “manejo integrado”. Foram incluídos artigos científicos sobre estudos realizados na América Latina, publicados de 2011 a 2017, com acesso livre ao texto integral e publicação em inglês, espanhol ou português. Foram coletados dados relativo aos autores, delineamento, amostra, principais resultados, país e ano da publicação. Finalmente, os estudos foram classificados em níveis de evidência.Resultados.Foram incluídos 20 estudos, dos quais 60% apresentaram baixa evidência científica (nível IV). Conforme esses estudos, os pacientes com diabetes possuem maior risco de desenvolver tuberculose, especialmente aqueles com controle glicêmico ineficaz. Além disso, pacientes com tuberculose-diabetes apresentam atraso na conversão do escarro e maior probabilidade de falha terapêutica e morte. Há maior prevalência da associação tuberculose-diabetes no sexo masculino. Em relação aos registros de tuberculose e diabetes em prontuários ou fichas eletrônicas de informação nos serviços de saúde, há falhas ou ausência de anotações. Foi identificado alto custo financeiro do manejo clínico em indivíduos com a comorbidade. A equipe multidisciplinar possui papel imprescindível na prevenção e promoção em saúde, nos três níveis de atenção.Conclusão.O rastreamento bidirecional de tuberculose-diabetes poderá implicar em melhor controle desses agravos, principalmente em países em desenvolvimento e em áreas endêmicas para tuberculose.

Minipigs as neonatal animal model for tuberculosis vaccine efficacy testing

Abstract Many vaccines against childhood diseases are administered early after birth. Despite the fact that neonatal-infant immunity differs from adult immunity, vaccine development studies frequently test efficacy in adult rather than in neonatal animal models. A good example of this scenario is Bacillus Calmette-Guerin (BCG). BCG is the only vaccine available against tuberculosis (TB). The vaccine lacks efficacy against child and adulthood pulmonary disease or reactivation of latent TB but prevents disseminated TB in children and is thus widely used in countries with endemic TB as part of the neonatal vaccine regimen. There are several new vaccines that have shown efficacy against TB in adult animal models yet fail to protect infants from TB disease in clinical trials. In this novel approach, we used the minipig as a neonatal animal model for evaluation of immune responses to BCG vaccination. The longitudinal immune responses of neonatal mini-piglets vaccinated with BCG were followed until adolescence, with the same monitoring applied to a group of unvaccinated mini-piglets. We characterized the memory and activation phenotype of T cells, cytokine profile, and monocyte activation in response to BCG stimulation from 4 weeks of age into adolescence- age of 24 weeks. Further, we challenged both vaccinated and non-vaccinated animals via aerosol route with a low dose aerosol of Mycobacterium tuberculosis strain HN878 and we characterized changes between the two groups in the course of immune responses following challenge. Based on comparison of immune responses to BCG in minipigs with similar studies in infants, our findings suggest that minipigs have the potential to serve as an effective neonatal animal model for vaccine development.

Statistical Method to Detect Tuberculosis Outbreaks among Endemic Clusters in a Low-Incidence Setting.

We previously reported use of genotype surveillance data to predict outbreaks among incident tuberculosis clusters. We propose a method to detect possible outbreaks among endemic tuberculosis clusters. We detected 15 possible outbreaks, of which 10 had epidemiologic data or whole-genome sequencing results. Eight outbreaks were corroborated.

Efficiency of IgM Anti-Cardiolipin Serum Level Screening for Monitoring Response to Anti-Tuberculosis Treatment in Comparison with Sputum Smear Conversion Test

Background: Two original methods for evaluation of response to tuberculosis treatment are sputum smear and culture. Sputum smear test has a low sensitivity and sputum culture is not available in many countries with endemic tuberculosis. There are some biomarkers diseases such as IgM anti-cardiolipin antibody which could be assessed for this purpose. Objectives: Therefore, we decided to measure the reduction rate of IgM anti-cardiolipin antibody during treatment of smear positive pulmonary tuberculosis (PTB) patients for monitoring response to treatment and then compare efficiency of this test with sputum smear conversion. Methods: In this research study 30 sputum smear positive PTB patients were included by convenient sampling method and then their serum samples were taken before and after the first 3 months of anti-TB treatment for measurement of IgM anti-cardiolipin antibody serum level by Elisa method. Their serum level changes during treatment were analyzed by paired t test with SPSS software (ver.18). Results: The mean IgM anti-cardiolipin serum level during treatment showed significant reduction relative to its level at baseline in 27 (90%) of total patients (P < 0.0001). Also, this result was confirmed in both cavitary (P < 0.0001) and non-cavitary (P = 0.005) groups. The sensitivity of test (90%) was equal with sputum smear conversion rate in our study (90%) and was associated with clinical improvement in all of 30 cases (100%). Conclusions: The reduction of IgM anti cardiolipin serum level during treatment, could be a reliable indicator of effective treatment and specially it may be applicable in PTB patients who have negative sputum smear test or cannot deliver sufficient sputum for evaluation of response to anti-TB treatment.

Single Pulmonary Nodule Management: Experience of a Moroccan Center about 24 Patients

Introduction: The management of single pulmonary nodule remains difficult, since it is of multiple etiologies. The endemicity of tuberculosis and hydatidosis in our context makes the etiological orientation even more difficult. Materials and Methods: This is a retrospective study, involving 24 patients, all operated on for a single pulmonary nodule in the department of thoracic surgery of CHU Hassan II of Fez over a period of 8 years. Results: There were 15 men and 9 women, with an average age of 51 years. 45.4% of patients had a history of known neoplasia. Discovery was fortuitous in 54% of cases. The radiologic diagnosis based on thoracic computed tomography had objectified an isolated nodule in all the patients with a right localization in 71% of the cases It was a solid pulmonary nodule in 91.5% of cases, and a frosted glass appearance in 8.5%. Bronchial fibroscopy was contributory in one case which was a carcinoid tumor. The approach was a conservative postero-lateral thoracotomy in 22 patients. The gesture was atypical resection in 67%, and lobectomy in 24.5% of cases, in the context of centrilobular nodules. The etiologies were dominated by pulmonary metastases in 29% of cases, pulmonary tuberculosis in 21% of cases. The postoperative course was simple in all patients. Conclusion: The pathological antecedents and the characteristics of the nodule on the imaging are essential elements allowing an etiological orientation. However, the pathological study remains the only method to confirm the diagnosis.