Perspectives from the 2nd International Post-Tuberculosis Symposium: mobilising advocacy and research for improved outcomes.

In 2020, it was estimated that there were 155 million survivors of TB alive, all at risk of possible post TB disability. The 2nd International Post-Tuberculosis Symposium (Stellenbosch, South Africa) was held to increase global awareness and empower TB-affected communities to play an active role in driving the agenda. We aimed to update knowledge on post-TB life and illness, identify research priorities, build research collaborations and highlight the need to embed lung health outcomes in clinical TB trials and programmatic TB care services. The symposium was a multidisciplinary meeting that included clinicians, researchers, TB survivors, funders and policy makers. Ten academic working groups set their own goals and covered the following thematic areas: 1) patient engagement and perspectives; 2) epidemiology and modelling; 3) pathogenesis of post-TB sequelae; 4) post-TB lung disease; 5) cardiovascular and pulmonary vascular complications; 6) neuromuscular & skeletal complications; 7) paediatric complications; 8) economic-social and psychological (ESP) consequences; 9) prevention, treatment and management; 10) advocacy, policy and stakeholder engagement. The working groups provided important updates for their respective fields, highlighted research priorities, and made progress towards the standardisation and alignment of post-TB outcomes and definitions.

En 2020, il est estimé qu'il y a 155 millions de survivants de la TB dans le monde, tous exposés à un risque d'invalidité post-TB. Le deuxième Symposium International Post-Tuberculose (Stellenbosch, Afrique du Sud) a été organisé dans le but de sensibiliser davantage à l'échelle mondiale et de permettre aux communautés touchées par la TB de contribuer activement à la mise en œuvre de l'agenda. De plus, nous avons entrepris de mettre à jour les connaissances sur la vie et les maladies post-TB, de déterminer les domaines de recherche prioritaires, d'établir des partenariats de recherche et de souligner l'importance d'intégrer les résultats sur la santé pulmonaire dans les essais cliniques et les services de soins de la TB. Le symposium était une réunion de travail pluridisciplinaire rassemblant des praticiens, des chercheurs, des personnes ayant survécu à la TB, des donateurs, des décideurs politiques et d'autres acteurs clés. Dix groupes de travail académiques ont établi leurs propres objectifs et ont abordé les sujets thématiques suivants : 1) engagement et perspectives des patients ; 2) épidémiologie et modélisation ; 3) pathogénie des séquelles post-TB ; 4) maladie pulmonaire post-TB (PTLD, pour l'anglais «post-TB lung disease ¼) ; 5) complications cardiovasculaires et vasculaires pulmonaires ; 6) complications neuromusculaires et squelettiques ; 7) complications pédiatriques ; 8) conséquences économiques, sociales et psychologiques (ESP, pour l'anglais «economic-social and psychological¼) ; 9) prévention, traitement et gestion ; 10) plaidoyer, politique et engagement des parties prenantes. Les groupes de travail académiques ont apporté des mises à jour significatives dans leurs domaines respectifs, ont mis en évidence les priorités de recherche et ont avancé vers la normalisation et l'harmonisation des résultats et des définitions de la post-TB.

Temperature variations during bone removal procedures similar to third molar extraction using different instruments.

Bone removal is commonly used in the extraction of third molars and the heat generated during the process can interfere with the repair of bone. The aim of this study was to evaluate the temperature variation presented in bone removal performed with a high-speed turbine (400000 rpm), implant motor with straight piece (100000 rpm), low-speed micromotor (20000 rpm) and piezoelectric saw (30 kHz) in pig mandibles. For this, bone removal was carried out around 20 posterior teeth, under constant saline solution irrigation with a syringe and needle. In addition, the time required to perform bone removal was recorded. The results indicated a mean (SD) temperature variation of 0.96 °C (0.6 °C) for the high-speed turbine, 1.38 °C (0.5 °C) with the implant motor, 2.22 °C (0.7 °C) for the low-speed micromotor and 2.90 °C (1.3 °C) for the piezoelectric saw. The conventional variance was calculated discounting the variation of time used for bone removal around the teeth. There was a statistically significant difference in temperature variation between the high-speed turbine vs the micromotor (p = 0.009) and the high speed micromotor vs the piezoelectric saw (p = 0.04). We conclude that there is a statistically significant difference in temperature variation between the instruments used in oral and maxillofacial surgery, with higher rotation speeds resulting in the lowest temperature variations and a reduced surgical time.

The effect of TB treatment on health-related quality of life for people with advanced HIV.

BACKGROUND: Study A5274 was an open-label trial of people with HIV (PLHIV) with CD4 cell count <50 cells/µL who were randomized to empirical TB treatment vs. isoniazid preventive therapy (IPT) in addition to antiretroviral therapy (ART). We evaluated health-related quality of life (HRQoL) by study arm, changes over time, and association with sociodemographic and clinical factors.METHODS: Participants aged >13 years were enrolled from outpatient clinics in 10 countries. HRQoL was assessed at Weeks 0, 8, 24 and 96 with questions about daily activity, hospital or emergency room visits, and general health status. We used logistic regression to examine HRQoL by arm and association with sociodemographic and clinical factors.RESULTS: Among 850 participants (424 empiric arm, 426 IPT arm), HRQoL improved over time with no difference between arms. At baseline and Week 24, participants with WHO Stage 3 or 4 events, or those who had Grade 3 or 4 signs/symptoms, were significantly more likely to report poor HRQoL using the composite of four HRQoL measures.CONCLUSION: HRQoL improved substantially in both arms during the study period. These findings show that ART, TB screening, and IPT can not only reduce mortality, but also improve HRQoL in PLHIV with advanced disease.

Outcomes in HIV-infected adults with tuberculosis at clinics with and without co-located HIV clinics in Botswana.

SETTING: Gaborone, Botswana. OBJECTIVE: To determine if starting anti-tuberculosis treatment at clinics in Gaborone without co-located human immunodeficiency virus (HIV) clinics would delay time to highly active antiretroviral therapy (HAART) initiation and be associated with lower survival compared to starting anti-tuberculosis treatment at clinics with on-site HIV clinics. DESIGN: Retrospective cohort study. Subjects were HAART-naïve, aged ≥ 21 years with pulmonary tuberculosis (TB), HIV and CD4 counts ≤ 250 cells/mm(3) initiating anti-tuberculosis treatment between 2005 and 2010. Survival at completion of anti-tuberculosis treatment or at 6 months post-treatment initiation and time to HAART after anti-tuberculosis treatment initiation were compared by clinic type. RESULTS: Respectively 259 and 80 patients from clinics without and with on-site HIV facilities qualified for the study. Age, sex, CD4, baseline sputum smears and loss to follow-up rate were similar by clinic type. Mortality did not differ between clinics without or with on-site HIV clinics (20/250, 8.0% vs. 8/79, 10.1%, relative risk 0.79, 95%CI 0.36-1.72), nor did median time to HAART initiation (respectively 63 and 66 days, P = 0.53). CONCLUSION: In urban areas where TB and HIV programs are separate, geographic co-location alone without further integration may not reduce mortality or time to HAART initiation among co-infected patients.

Yield of contact tracing from pediatric tuberculosis index cases in Gaborone, Botswana.

SETTING: Contact tracing using pediatric index cases has not been adequately investigated in high tuberculosis (TB) and human immunodeficiency virus (HIV) prevalence settings. OBJECTIVE: To determine the yield of contact tracing in household contacts of pediatric TB index cases in Botswana. DESIGN: Index cases included all pediatric (age ≤ 13 years) TB admissions from January 2009 to December 2011 to Botswana's largest referral hospital. A contact tracing team identified cases, conducted home visits, symptom-screened contacts and referred those with ≥ 1 TB symptoms. The primary outcome was newly diagnosed TB in a contact. RESULTS: From 163 pediatric index cases, 548 contacts were screened (median 3 contacts/case, interquartile range [IQR] 2-4). Of these, 49 (9%) were referred for positive symptoms on screening and 27/49 (55%) were evaluated for active TB. Twelve new TB cases were diagnosed (12/548, 2.2%); the median age was 31 years (IQR 23-38); 11 (92%) were smear-positive. Ten (83%) had known HIV status: 7 (70%) were HIV-positive. To find one new TB case, the number needed to contact trace (index cases/new cases) was 13.6, and the number needed to screen (contacts/new cases) was 46. CONCLUSION: This yield of contact tracing using pediatric index cases is similar to the traditional adult index case approach. Improving the proportion of symptomatic contacts evaluated may increase yield.

Impact of the human immunodeficiency virus on early multidrug-resistant tuberculosis treatment outcomes in Botswana.

SETTING: The impact of the human immunodeficiency virus (HIV) on multidrug-resistant tuberculosis (MDR-TB) treatment outcomes in sub-Saharan Africa, where extensive rollout of highly active antiretroviral therapy (HAART) has occurred, remains unclear. OBJECTIVE: To compare the time to initial culture conversion among patients with and those without HIV infection in a setting of individualized MDR-TB care in Botswana. DESIGN: Prospective cohort study of MDR-TB patients receiving ambulatory, integrated TB-HIV care at two public clinics in Botswana. The time to culture conversion was compared by HIV status using Cox proportional hazard ratios (HRs). RESULTS: A total of 40 HIV-infected and 30 non-HIV-infected patients with MDR-TB and follow-up cultures were identified. The median time to initial culture conversion was 78 days (interquartile range [IQR] 42-186) for HIV-infected and 95 days (IQR 70-133) for non-HIV-infected individuals (log rank P > 0.5; unadjusted HR 0.9, 95%CI 0.5-1.5). Adjusting for age, sex, treatment history and number of active anti-tuberculosis drugs did not change this result (adjusted HR 0.8, 95%CI 0.4-1.4). CONCLUSION: We found no difference in the proportion of or time to initial sputum culture conversion between an HIV-infected and a non-infected cohort of MDR-TB patients in Botswana, suggesting that outcomes may be comparable in similar settings with access to individualized anti-tuberculosis treatment and HAART.

Alcohol use and abuse among patients with multidrug-resistant tuberculosis in Botswana.

BACKGROUND: Data on alcohol abuse as a risk factor for the development of multidrug-resistant tuberculosis (MDR-TB) are scarce. OBJECTIVE: To describe the patterns of alcohol use in MDR-TB patients and to determine whether alcohol use is associated with the development of MDR-TB in Botswana. METHODS: We compared the level of alcohol use among MDR-TB patients against three control groups: 1) non-MDR-TB patients, 2) human immunodeficiency virus (HIV) infected patients without a history of TB, and 3) the general population. Alcohol use and abuse was measured with the Alcohol Use Disorders Identification Test 10 (AUDIT) questionnaire. RESULTS: Of a total national population of 164 MDR-TB cases, 114 (70%) were interviewed. MDR-TB cases had a lifetime prevalence of alcohol use of 35.1%, which was lower than that of all control groups (P < 0.001). MDR-TB cases had higher 1-month prevalence of alcohol dependence symptoms and a lower 1-year period prevalence of alcohol dependence symptoms (P < 0.01 and P = 0.01 respectively). Among patients with TB, alcohol abuse was found to be a risk factor for the development of MDR-TB. CONCLUSION: MDR-TB patients in Botswana have high rates of alcohol use and abuse. Among TB patients, alcohol abuse is associated with the diagnosis of MDR-TB, and could be an important modifiable factor.

Nonclassic measles infections in an immune population exposed to measles during a college bus trip.

This study investigated the frequency of mild or asymptomatic measles infections among 44 persons exposed to a student with measles during a 3-day bus trip using two buses. Questionnaires and serum samples were obtained 26-37 days after the trip. All participants had detectable measles-neutralizing antibodies, and none developed classic measles symptoms. Ten persons (23%) were IgM positive for measles, indicating recent infection. Among previously vaccinated IgM-negative persons, those who rode on bus A with the index case-patient had significantly higher microneutralization titers than those on bus B (P= .001), suggesting that some persons on bus A were infected but were IgM negative at the time of the study. Mild or asymptomatic measles infections are probably very common among measles-immune persons exposed to measles cases and may be the most common manifestation of measles during outbreaks in highly immune populations.

Preoperative localization of parathyroid lesions in hyperparathyroidism: relationship between technetium-99m-MIBI uptake and oxyphil cell content.

UNLABELLED: The aim of this study was to assess the relationship between parathyroid oxyphil cell content and early or late phases of uptake of 99mTc-MIBI, a radioisotope preferentially retained in mitochondria-rich cells. METHODS: This study is a retrospective, single-blind analysis of all double-phase 99mTc-MIBI parathyroid scintigraphy studies performed before surgery in our institution between 1990 and 1995. A total of 18 parathyroid lesions in 14 patients were reviewed. This sample included 11 cases of primary hyperparathyroidism (8 adenomas, 1 adenocarcinoma and 2 hyperplasias) and 3 cases of tertiary hyperparathyroidism secondary to chronic renal failure. RESULTS: Uptake of 99mTc-MIBI in the early phase of scintigraphy was associated with larger parathyroid lesions (1.61 +/- 1.61 ml versus 0.33 +/- 0.27 ml; p < 0.02) and higher serum calcium levels (3.00 +/- 0.41 mM versus 2.67 +/- 0.14 mM; p < 0.02). More importantly, we found that a parathyroid oxyphil cell content greater than 25% was more often associated with a positive uptake of 99mTc-MIBI in the late phase of the test (positive late uptake in 78% of lesions with a high oxyphil cell content versus 33% in lesions with an oxyphil cell content between 1% and 25% and 0% in lesions with no oxyphil cells; p < 0.04). CONCLUSION: These findings suggest that the late retention of 99mTc-MIBI in double-phase scintigraphy is related to parathyroid oxyphil cell content.

Schnitzler's syndrome.

We report on a case of Schnitzler's syndrome, focusing on pattern of bone involvement and its differential diagnosis.

Rapid washout of technetium-99m-MIBI from a large parathyroid adenoma.

We report a case of rapid 99mTc-methoxyisobutylisonitrile (MIBI) clearance from a parathyroid adenoma. A double-phase 99mTc-MIBI parathyroid scintigraphy was performed on a 62-yr-old female evaluated for primary hyperparathyroidism. A large parathyroid adenoma was visualized caudal to the left lobe of the thyroid gland with an unusually rapid washout of the tracer from tumor tissue. Histologic tissue examination confirmed the presence of a parathyroid adenoma and the absence of oxyphil cells. Care should be taken in interpretation of 99mTc-MIBI parathyroid scintigrams because some adenomas can present a rapid release of the radiotracer in a double-phase study. Technetium-99m-MIBI retention could be related to the number of mitochondria-rich cells in parathyroid adenomas or to hyperplasia.

Cooperative computer system for genome sequence analysis.

Analysis of the huge volumes of data generated by large scale sequencing projects clearly requires the construction of new sophisticated computer systems. These systems should be able to handle the biological data as well as the results of the analysis of this data. They should also help the user to choose the most appropriate method for a simple task and to string together the methods needed to solve a global analysis task. In this paper we present the prototype of a software system that provides an environment for the analysis of large-scale sequence data. In a first approach this environment has been put to the test within the B. subtilis sequencing project. This system integrates both a descriptive knowledge of the entities involved (genes, regulatory signals etc.) and the methodological knowledge concerning an extendable set of analytical methods (i.e. how to solve a sequence analysis problem through task decomposition and method selection). A knowledge representation based on two existing object-oriented models, named Shirka and SCARP, is used to implement this integrated system. In addition, the present prototype provides a suitable user interface for both displaying the results generated by several methods and interacting with the objects. We present in this paper an overview of the knowledge-based models used to build this integrated system, and a description of the way in which biological entities and sequence analysis tasks are represented. We give illustrations of the co-operation between user and system during the problem solving process. Such a system constitutes a computer workbench for molecular biologists studying the genetic programs of living organisms.

APIC: a generic interface for sequencing projects.

In this paper, we describe the APIC graphical interface that aims at displaying the results produced by the genomic sequence analysis methods and at helping a comparison of these results. The major feature of APIC lies in its genericity. As a matter of fact, this interface can obviously be used to visualise genetic or physical maps but it also able to display other kinds of information such as curves or pictures. On the one hand, APIC provides the biologist who builds a new sequence analysis method with a standard interface allowing to display his results. Thus, he can avoid implementing a specific visualisation tool. On the other hand, even when the methods already have their own interfaces, using APIC has the advantage of giving a homogeneous way to compare several results coming from different analysis tools. Moreover, it provides some powerful functions for navigating and browsing into the results.

Evaluation of a 99mTc-antimyosin kit for myocardial infarct imaging.

The Fab fragment of a mouse monoclonal antibody AM(3-48) that recognizes alpha and beta-heavy chains of human atrial and ventricular myosin and beta-heavy chain of human slow skeletal muscle myosin [CardioVisionTM] was labeled with 99mTc using stannous reductant in a simple, instant kit method. The infarcted heart uptake in dogs of 99mTc-AM(3-48)Fab' was compared with that of established radiopharmaceuticals routinely used for cardiac imaging in humans. The dog infarct was induced by bringing a catheter from the femoral artery to the coronary artery where an artificial blood clot was generated. The 99mTc-AM(3-48)Fab' preparation was selectively taken up by infarcted myocardium, resulting in diagnostic quality images of the infarcted area as early as 6 hour post-injection, rendering CardioVisionTM particularly useful for SPECT imaging. Good agreement was found between the images obtained with 99mTc-Pyrophosphate and those obtained with 99mTc-AM(3-48)Fab', while the infarcted area was clearly delineated as a cold spot with 99mTc-MIBI or 201 Tl-thallous chloride. The biodistribution of 99mTc-AM(3-48)Fab' was also studied in healthy and isoproterenol-infarcted rats, from which dosimetry values in man were extrapolated. The data indicate that the kidneys will receive the highest radiation dose and that they will be the main contributors to the total radiation burden, which was estimated at 0.005 rad/mCi.

Myocardial technetium 99m-labeled sestamibi single-photon emission computed tomographic imaging in the detection of coronary artery disease: comparison between early (15 minutes) and delayed (60 minutes) imaging.

BACKGROUND: Previous studies have demonstrated that there is a "partial" myocardial redistribution of 99mTc-labeled sestamibi (MIBI) between 1 and 3 hours after intravenous injection at stress. The purpose of this prospective study was to compare MIBI single-photon emission computed tomographic (SPECT) imaging performed 15 and 60 minutes after the injection at stress in the detection of coronary artery disease. METHODS AND RESULTS: Thirty-five patients with coronary artery disease (26 underwent coronary angiography and 23 had a positive 201Tl study result) were included in this study. SPECT imaging started 15 minutes after the injection of 25 to 30 mCi MIBI at peak stress (180-degree arc, 32 angles, 25 sec/view, and high-resolution collimator). Patients underwent reimaging at 60 minutes according to the same protocol and with the same gamma camera. A rest study was obtained 75 minutes after the injection of MIBI (25 to 30 mCi) at rest, 48 hours later. Images (divided for a total of 19 segments per patient) were interpreted by two blinded observers for patient diagnosis and segmental comparison. The patient diagnosis was the same for the two protocols: normal = 3, ischemia = 27, and scar = 5. The segmental agreement (kappa = 0.90) was 632/665 (95.0%). The imaging performed at 15 minutes detected normal, ischemia, and scar in 413, 189, and 63 segments, respectively, whereas the imaging performed at 60 minutes detected 422, 180, and 63 segments, respectively (difference not significant). The early and delayed images were placed side by side for subjective comparison of the extent of the defect. Early imaging showed slightly larger defects in six patients, equal defects in 24 patients, and slightly smaller defects in five patients. Ischemic/normal wall ratios were 0.67 +/- 0.16 at 15 minutes and 0.68 +/- 0.15 at 60 minutes. CONCLUSIONS: There is no clinically significant difference between SPECT imaging performed at 15 minutes or 60 minutes after the injection of MIBI at stress. Furthermore, this study showed that it is feasible to obtain good-quality MIBI images even 15 minutes after the injection at stress.

Thallium-201-dipyridamole imaging: comparison between a standard dose and a high dose of dipyridamole in the detection of coronary artery disease.

UNLABELLED: The purpose of this study was to compare two different doses of dipyridamole as a pharmacologic stress test for 201Tl imaging. METHODS: Twenty-four patients with significant coronary artery disease (15 had undergone a coronary angiogram and 9 had undergone a previous 201Tl study with a significant lesion) were prospectively studied. Within 1 wk, all patients underwent two 201T-dipyridamole myocardial planar studies, one using a standard dose (STD) and the other, a high dose (HIGH) of dipyridamole. The protocol order was randomly assigned. The STD protocol used a dose of 0.14 mg/kg/min for a duration of 4 min (0.56 mg/kg), and the HIGH protocol used a dose of 0.14 mg/kg min for a duration of 6 min (0.84 mg/kg). The 201Tl was injected 3 min after the end of the dipyridamole infusion. Images, obtained 5 min and 4 hr later, were interpreted (divided into five segments each) by three blinded observers. RESULTS: The STD protocol showed normal, ischemia and scar in 252, 91 and 17 segments, respectively. The HIGH protocol detected 232, 118 and 10 segments, respectively. A side-by-side evaluation was done to evaluate the defect extent subjectively, which was greater with HIGH in 14, equal in six and smaller in four patients. One or more side effects were seen in 14 patients with STD and in 19 with HIGH. Increased heart rate (8 bpm for STD and 19 bpm for HIGH, p < 0.001) was the only significant change seen in the hemodynamic parameters. CONCLUSION: This preliminary study indicates that a high dose of dipyridamole seems to be safe and can be helpful to increase the sensitivity of 201Tl imaging.

Massive hydrothorax complicating peritoneal dialysis. Isotopic investigation (peritoneopleural scintigraphy).

Massive hydrothorax occurring during continuous ambulatory peritoneal dialysis is a rare complication that may appear at any time during the course of the treatment. Most of the time, it is right-sided and is more frequent in female patients. A case is presented that was investigated by peritoneopleural scintigraphy. A rapid accumulation of the radiopharmaceutical over the right hemithorax was observed. To explain that finding, a macroscopic diaphragmatic defect was suspected. Different therapeutic approaches are presented.