Sero-epidemiological assessment of Chlamydia trachomatis infection and sub-fertility in Samoan women.

BACKGROUND: In our recent village-based cross-sectional study, the prevalence of nucleic acid amplification technique (NAAT) diagnosed Chlamydia trachomatis (CT) in sexually active Samoan women was very high (36 %), and test positivity was associated with sub-fertility. We conducted a serological and epidemiological analysis in these participants to identify if serological data can provide further insight into the potential contribution of CT to sub-fertility in this population. METHODS: Serological prediction of CT associated sub-fertility was conducted using a series of commercial tests. The correlation between fertility or sub-fertility, behavioral factors, and serologically predicted CT associated sub-fertility was determined. RESULTS: A positive antibody reaction against the Chlamydia Major Outer Membrane Protein (MOMP) was significantly associated with sub-fertility, with 50 % of infertile women being positive. Serum IgG and IgA antibodies against MOMP correlated with current infection measured by urine NAAT, suggesting longer term infections are common in this population. Chlamydia pneumoniae antibodies were frequently detected in this population (84 %), and unexpectedly, were significantly associated with sub-fertility. CONCLUSIONS: The high prevalence of chlamydial infection and of positive chlamydial sub-fertility results suggests that CT is an important and frequent contributory factor to sub-fertility in this population.

Skin pigmentation interferes with the clinical measurement of regional cerebral oxygen saturation.

BACKGROUND: Devices utilizing near-infrared (NIR) spectroscopy have been used to assess regional intracerebral oxygen saturation (rSO2) during anaesthesia for a decade. The presence of wide differences among individuals reduces their applicability to steady-state measurements. Current devices may not adequately account for variations in skin pigmentation. METHODS: From our ongoing departmental registry, 3282 consecutive patients underwent cardiac surgery between 2010 and 2012 and their pre-induction measurements of rSO2 were available. Of these, 2096 identified themselves as Caucasian (Cauc) and 1186 as African-American (AA). Pre-induction rSO2, clinical and operative features were compared. RESULTS: Clinical and operative details of these patients differed widely between the two populations. High-risk features were more common in AA patients, but no difference in mortality was observed (4.8% in AAs vs 4.7% in Caucs, P=0.87). Preprocedure rSO2 was systematically higher in Cauc (65.5% vs 53.3%, P<0.001). After multivariate linear regression adjustment, AA ethnicity proved to be associated independently with low rSO2 [odds ratio (OR) -8.28, 95% confidence interval (CI) -9.12 to -7.44, P<0.001]. Multivariate logistic regression analysis showed that preprocedural rSO2 was independently associated with operative mortality both in the Cauc group (OR 0.97, 95% CI 0.96-0.99, P=0.001) and in the AA group (OR 0.97, 95% CI 0.95-0.99, P=0.01). CONCLUSIONS: AAs have a lower rSO2 than Caucs as measured by the INVOS 5100C cerebral oximeter. Reasonably, this could be attributed to attenuation of the NIR light by skin pigment. Despite this limitation, in both ethnic groups, lower preoperative rSO2 was predictive of greater operative mortality.

Epiregulin (EREG) and human V-ATPase (TCIRG1): genetic variation, ethnicity and pulmonary tuberculosis susceptibility in Guinea-Bissau and The Gambia.

We analyzed two West African samples (Guinea-Bissau: n=289 cases and 322 controls; The Gambia: n=240 cases and 248 controls) to evaluate single-nucleotide polymorphisms (SNPs) in Epiregulin (EREG) and V-ATPase (T-cell immune regulator 1 (TCIRG1)) using single and multilocus analyses to determine whether previously described associations with pulmonary tuberculosis (PTB) in Vietnamese and Italians would replicate in African populations. We did not detect any significant single locus or haplotype associations in either sample. We also performed exploratory pairwise interaction analyses using Visualization of Statistical Epistasis Networks (ViSEN), a novel method to detect only interactions among multiple variables, to elucidate possible interaction effects between SNPs and demographic factors. Although we found no strong evidence of marginal effects, there were several significant pairwise interactions that were identified in either the Guinea-Bissau or the Gambian samples, two of which replicated across populations. Our results indicate that the effects of EREG and TCIRG1 variants on PTB susceptibility, to the extent that they exist, are dependent on gene-gene interactions in West African populations as detected with ViSEN. In addition, epistatic effects are likely to be influenced by inter- and intra-population differences in genetic or environmental context and/or the mycobacterial lineages causing disease.

Diabetes characteristics and long-term management needs in diabetic TB patients.

BACKGROUND: Diabetes mellitus (DM) is common among patients with TB. We assessed DM characteristics and long-term needs of DM-TB patients after completing TB treatment.METHODS: Newly diagnosed TB patients with DM were recruited for screening in a randomised clinical trial evaluating a simple algorithm to improve glycaemic control during TB treatment. DM characteristics, lifestyle and medication were compared before and after TB treatment and 6 months later. Risk of cardiovascular disease (CVD), albuminuria and neuropathy were assessed after TB treatment.RESULTS: Of 218 TB-DM patients identified, 170 (78%) were followed up. Half were males, the mean age was 53 years, 26.5% were newly diagnosed DM. High glycated haemoglobin at TB diagnosis (median 11.2%) decreased during TB treatment (to 7.4% with intensified management and 8.4% with standard care), but this effect was lost 6 months later (9.3%). Hypertension and dyslipidemia contributed to a high 10-year CVD risk (32.9% at month 6 and 35.5% at month 12). Neuropathy (33.8%) and albuminuria (61.3%) were common. After TB treatment, few patients used CVD-mitigating drugs.CONCLUSION: DM in TB-DM patients is characterised by poor glycaemic control, high CVD risk, and nephropathy. TB treatment provides opportunities for better DM management, but effort is needed to improve long-term care.

Effect of age and vaccination with a pneumococcal conjugate vaccine on the density of pneumococcal nasopharyngeal carriage.

BACKGROUND: This study evaluated the impact of age and pneumococcal vaccination on the density of pneumococcal nasopharyngeal carriage. METHODS: A cluster-randomized trial was conducted in rural Gambia. In 11 villages (the vaccine group), all residents received 7-valent pneumococcal conjugate vaccine (PCV-7), while in another 10 villages (the control group), only children <30 months old or born during the study period received PCV-7. Cross-sectional surveys (CSSs) were conducted to collect nasopharyngeal swabs before vaccination (baseline CSS) and 4, 12, and 22 months after vaccination. Pneumococcal density was defined using a semiquantitative classification (range, 1-4) among colonized individuals. An age-trend analysis of density was conducted using data from the baseline CSS. Mean pneumococcal density was compared in CSSs conducted before and after vaccination. RESULTS: Mean bacterial density among colonized individuals in the baseline CSS was 2.57 for vaccine-type (VT) and non-vaccine-type (NVT) pneumococci; it decreased with age (P < .001 for VT and NVT). There was a decrease in the density of VT carriage following vaccination in individuals older than 5 years (from 2.44 to 1.88; P = .001) and in younger individuals (from 2.57 to 2.11; P = .070) in the vaccinated villages. Similar decreases in density were observed with NVT within vaccinated and control villages. No significant differences were found between vaccinated and control villages in the postvaccination comparisons for either VT or NVT. CONCLUSIONS: A high density of carriage among young subjects might partly explain why children are more efficient than adults in pneumococcal transmission. PCV-7 vaccination lowered the density of VT and of NVT pneumococcal carriage in the before-after vaccination analysis. CLINICAL TRIALS REGISTRATION: ISRCTN51695599.

Implementing the 4R and 9H regimens for TB preventive treatment in Indonesia.

BACKGROUND: The implementation of tuberculosis preventive treatment (TPT) is challenging especially in resource-limited settings. As part of a Phase 3 trial on TPT, we described our experience with the use of rifampicin for 4 months (4R) and isoniazid for 9 months (9H) in Indonesia.METHODS: In 2011-2017, children and adults with latent TB infection were randomised to either 4R or 9H and followed until 16 months after randomisation for children and 28 months for adults. The primary outcome was the treatment completion rate. Secondary outcomes were Grade 3-5 adverse events (AEs), active TB occurrence, and health costs.RESULTS: A total of 157 children and 860 adults were enrolled. The 4R treatment completion rate was significantly higher than that of 9H (78.7% vs. 65.5%), for a rate difference of 13.2% (95% CI 7.1-19.2). No Grade 3-5 AEs were reported in children; in adults, it was lower in 4R (0.4%) compared to 9H (2.8%). The incidence of active TB was lower with 4R than with 9H (0.09/100 person-year vs. 0.36/100 person-year) (rate difference: -0.36/100 person-year). The total cost per patient was lower for the 4R regimen than for the 9H regimen (USD151.9 vs. USD179.4 in adults and USD152.9 vs. USD206.5 in children)CONCLUSIONS: Completion and efficacy rates for 4R were better than for 9H. Compared to 9H, 4R was cheaper in all age groups, safer in adults and equally safe in children. The Indonesian TB program could benefit from these benefits of the 4R regimen.

An axisymmetric meniscus converges particles for microscopy.

Capillary rise on a tapered cylindrical rod creates a static axisymmetric meniscus that quantitatively attracts buoyant particles into a single microscopic field of view, providing a new method for small particle microscopy. This approach simplifies the visualization of micrometre-sized particles, such as pollen and parasite eggs, and has potential utility in remote location monitoring and clinical diagnosis.

Educational counselling of patients with combined TB and diabetes mellitus: a randomised trial.

SETTING: Newly diagnosed pulmonary TB with diabetes mellitus (DM) comorbidity attending clinics in Bandung City, Indonesia. OBJECTIVE: To describe the effect of educational counselling on patients' knowledge about TB (transmission, treatment, risk factors) and DM (symptoms, treatment, complications, healthy lifestyle), adherence to medication, and to assess characteristics associated with knowledge. DESIGN: All patients received counselling and were then randomised to either structured education on TB-DM, combined with clinical monitoring and medication adjustment (intervention arm), or routine care (control arm). Knowledge and adherence were assessed using a questionnaire. RESULTS: Baseline and 6-month questionnaires were available for 108 of 150 patients randomised (60/76 in the intervention arm and 48/74 in the control arm). Patients knew less about DM than about TB. There was no significant difference in the proportion with knowledge improvement at 6 months, both for TB (difference of differences 14%; P = 0.20) or for DM (10%; P = 0.39) between arms. Intervention arm patients were more likely to adhere to taking DM medication, with fewer patients reporting ever missing oral DM drugs than those in the control arm (23% vs. 48%; P = 0.03). Higher education level was associated with good knowledge of both TB and DM. CONCLUSIONS: Structured education did not clearly improve patients' knowledge. It was associated with better adherence to DM medication, but this could not be attributed to education alone. More efforts are needed to improve patients' knowledge, especially regarding DM.

CONTEXTE: Patients atteints de diabète sucré (DM) ayant récemment reçu un diagnostic de TB pulmonaire consultant dans les cliniques de la ville de Bandung, Indonésie. OBJECTIF: Décrire l'effet de conseils éducatifs sur les connaissances des patients en matière de TB (transmission, traitement, facteurs de risque), de DM (symptômes, traitement, complications, mode de vie sain) et d'observance thérapeutique, et évaluer les caractéristiques associées à ces connaissances. MÉTHODE: Tous les patients ont reçu des conseils et ont ensuite été randomisés dans l'un des deux groupes suivants : programme d'éducation structuré sur la TB-DM associé à un suivi clinique et à un ajustement thérapeutique (groupe d'intervention) ou prise en charge de routine (groupe témoin). Les connaissances et l'observance ont été évaluées par questionnaire. RÉSULTATS: Les questionnaires administrés à l'inclusion et à 6 mois étaient disponibles pour 108 des 150 patients randomisés (60/76 dans le groupe d'intervention et 48/74 dans le groupe témoin). Les connaissances des patients étaient moins bonnes sur le DM que sur la TB. Aucune différence significative n'a été observée entre les groupes dans la proportion de patients dont les connaissances s'étaient améliorées à 6 mois, tant pour la TB (différence des différences 14% ; P = 0,20) que pour le DM (10% ; P = 0,39). Les patients du groupe d'intervention étaient plus susceptibles d'observer correctement leur traitement antidiabétique. Moins de patients ont en effet rapporté avoir manqué une dose de leur traitement antidiabétique oral par rapport au groupe témoin (23% vs. 48% ; P = 0,03). Un niveau d'éducation plus élevé a été associé à de bonnes connaissances sur la TB et le DM. CONCLUSIONS: Le programme d'éducation structuré n'a pas amélioré de manière évidente les connaissances des patients. Ce programme a été associé à une meilleure observance du traitement antidiabétique, mais cela n'a pas pu être attribué au seul programme d'éducation. Davantage d'efforts sont nécessaires pour améliorer les connaissances des patients, notamment sur le DM.

Spatial analysis of tuberculosis in an urban west African setting: is there evidence of clustering?

OBJECTIVES: To describe the pattern of tuberculosis (TB) occurrence in Greater Banjul, The Gambia with Geographical Information Systems (GIS) and Spatial Scan Statistics (SaTScan) and to determine whether there is significant TB case clustering. METHODS: In Greater Banjul, where 80% of all Gambian TB cases arise, all patients with TB registered at chest clinics between March 2007 and February 2008 were asked to participate. Demographic, clinical characteristics and GPS co-ordinates for the residence of each consenting TB case were recorded. A spatial scan statistic was used to identify purely spatial and space-time clusters of tuberculosis among permanent residents. RESULTS: Of 1145 recruited patients with TB, 84% were permanent residents with 88% living in 37 settlements that had complete maps available down to settlement level. Significant high- and low-rate spatial and space-time clusters were identified in two districts. The most likely cluster of high rate from both the purely spatial analysis and the retrospective space-time analysis were from the same geographical area. A significant secondary cluster was also identified in one of the densely populated areas of the study region. CONCLUSIONS: There is evidence of significant clustering of TB cases in Greater Banjul, The Gambia. Systematic use of cluster detection techniques for regular TB surveillance in The Gambia may aid effective deployment of resources. However, passive case detection dictates that community-based active case detection and risk factor surveys would help confirm the presence of true clusters and their causes.

Early chest X-ray in persons with presumptive tuberculosis increases Xpert® MTB/RIF diagnostic yield and efficiency.

Adult presumptive tuberculosis (TB) patients (n = 1690) were screened for TB using a questionnaire, chest X-ray (CXR) and sputum microscopy for acid-fast bacilli (AFB); Mycobacterium tuberculosis culture was performed for 74% of the patients and Xpert® MTB/RIF was done for 17.2%. Among patients recruited, 943 (55.8%) were diagnosed with TB, of whom 870 (92.3%) were bacteriologically confirmed and 73 (7.7%) were clinically diagnosed on the basis of CXR. Using CXR prior to culture or Xpert testing reduces the number needed to screen from 7.6 to 5.0. Using CXR to triage for culture or Xpert testing reduces the number of missed cases and increases the efficiency of culture and Xpert testing.

Des patients adultes présumés atteints de TB (n = 1690) ont été dépistés à l'aide d'un questionnaire, d'une radiographie pulmonaire (CXR) et d'une microscopie de crachats à la recherche des bacilles acido-alcoolo-résistants; une culture de Mycobacterium tuberculosis a été réalisée chez 74% des patients et un test Xpert® MTB/RIF, chez 17,2%. Parmi les patients recrutés, 943 (55,8%) ont eu un diagnostic de TB, dont 870 (92,3%) ont été confirmés par bactériologie et 73 (7,7%) ont été diagnostiqués sur la CXR. Recourir à la CXR avant la culture ou le test Xpert réduit le nombre requis pour dépister un cas de 7,6 à 5,0. L'utilisation de la CXR pour le triage avant la culture ou le test Xpert réduit les cas manqués et augmente l'efficacité de l'utilisation de la culture et de l'Xpert.

Se investigó de la tuberculosis (TB) en pacientes adultos con presunción clínica de la enfermedad (n = 1690) mediante un cuestionario, la radiografía de tórax (CXR) y la baciloscopia del esputo; se practicó el cultivo para Mycobacterium tuberculosis en 74% de los pacientes y la prueba Xpert® MTB/RIF en 17,2%. De los pacientes que participaron se diagnosticó la TB en 943 (55,8%), de los cuales 870 (92,3%) con confirmación bacteriológica y 73 (7,7%) con diagnóstico clínico a partir de la CXR. El hecho de realizar la CXR o la prueba Xpert antes del cultivo disminuye de 7,6 a 5,0 el número de pacientes que deben someterse a detección. El uso de la CXR para seleccionar los casos en que se debe practicar el cultivo o la prueba Xpert disminuye los casos pasados por alto y aumenta la eficiencia del uso del cultivo y la prueba Xpert.

A public health approach to increase treatment of latent TB among household contacts in Brazil.

SETTING: Two consecutive trials were conducted to evaluate the effectiveness of a public health approach to identify and correct problems in the care cascade for household contacts (HHCs) of TB patients in three Brazilian high TB incidence cities.METHODS: In the first trial, 12 clinics underwent standardised evaluation using questionnaires administered to TB patients, HHCs and healthcare workers, and analysis of the cascade of latent TB care among HHCs. Six clinics were then randomised to receive interventions to strengthen management of latent TB infection (LTBI), including in-service training provided by nurses, work process organisation and additional clinic-specific solutions. In the second trial, a similar but streamlined evaluation was conducted in two clinics, who then received initial and subsequent intensive in-service training provided by a physician.RESULTS: In the evaluation phase of both trials, many HHCs were identified, but few started LTBI treatment. After the intervention, the number of HHCs initiating treatment per 100 active TB patients increased by 10 (95%CI - 11 to 30) in the first trial, and by 44 (95%CI 26 to 61) in the second trial.DISCUSSION: A public health approach with standardised evaluation, local decisions for improvements, followed by intensive initial and in-service training appears promising for improved LTBI management.

T-cell assay conversions and reversions among household contacts of tuberculosis patients in rural India.

BACKGROUND: Interferon-gamma assays (IGRAs) are alternatives to the tuberculin skin test (TST), but IGRA conversions and reversions are not well understood. In a pilot study, we determined conversions and reversions using QuantiFERON-TB Gold In-Tube((R)) (QFT) among household contacts of TB cases, and evaluated the effect of using various definitions and criteria for conversions. DESIGN: In a cohort of 250 contacts in India, 46% were TST-positive at baseline and 54% were QFT-positive. We re-tested this cohort after 12 months. Conversion rates were estimated using several definitions. RESULTS: Of the 250 contacts, 205 (82%) underwent repeat testing. Among 85 contacts with baseline TST-negative/QFT-negative results, TST conversion rates ranged between 7.5% and 13.8%, and QFT conversion rates ranged between 11.8% and 21.2%, depending on the definitions used. Among 109 contacts who were QFT-positive at baseline, seven (6.4%) had QFT reversions. QFT reversions were most likely when the baseline TST was negative and QFT results were just above the diagnostic cut-off. CONCLUSIONS: QFT conversions and reversions occurred among contacts of TB cases. Conversion rates seemed to vary, depending on the test and definitions used for conversions. These findings need to be verified in larger studies in various settings.

Oxygen for treatment of severe pneumonia in The Gambia, West Africa: a situational analysis.

SETTING: Health facilities in The Gambia, West Africa. OBJECTIVES: Oxygen treatment is vital in pneumonia, the leading cause of death in children globally. There are shortages of oxygen in developing countries, but little information is available on the extent of the problem. We assessed national oxygen availability and use in The Gambia, a sub-Saharan African country. METHODS: A government-led team visited 12 health facilities in The Gambia. A modified World Health Organization assessment tool was used to determine oxygen requirements, current provision and capacity to support effective oxygen use. RESULTS: Eleven of the 12 facilities managed severe pneumonia. Oxygen was reliable in three facilities. Requirement and supply were often mismatched. Both oxygen concentrators and oxygen cylinders were used. Suboptimal electricity and maintenance made using concentrators difficult, while logistical problems and cost hampered cylinder use. Children were usually triaged by trained nurses who reported lack of training in oxygen use. Oxygen was given typically by nasal prongs; pulse oximetry was available in two facilities. CONCLUSIONS: National data showed that oxygen availability did not meet needs in most Gambian health facilities. Remedial options must be carefully assessed for real costs, reliability and site-by-site usability. Training is needed to support oxygen use and equipment maintenance.

Trained innate immunity and resistance to Mycobacterium tuberculosis infection.

BACKGROUND: Some individuals, even when heavily exposed to an infectious tuberculosis patient, develop neither active nor latent tuberculosis infection (LTBI). This 'early clearance' of Mycobacterium tuberculosis is associated with a history of bacillus Calmette-Guérin (BCG) vaccination. As BCG vaccination can boost innate immune responses through a process termed 'trained immunity', we hypothesize that BCG-induced trained innate immunity contributes to early clearance of M. tuberculosis. OBJECTIVES: We describe the epidemiological evidence and biological concepts of early clearance and trained immunity, and the possible relation between these two processes through BCG vaccination. SOURCES: Relevant data from published reports up to November 2018 were examined in the conduct of this review. CONTENT: Several observational studies and one recent randomized trial support the concept that boosting innate immunity contributes to protection against M. tuberculosis infection, with BCG vaccination providing approximately 50% protection. The molecular mechanisms mediating early clearance remain largely unknown, but we propose that trained immunity, characterized by epigenetic and metabolic reprogramming of innate immune cells such as monocytes or macrophages, is at least partially responsible for eliminating the mycobacteria and inducing early clearance. IMPLICATIONS: Future studies should examine if BCG revaccination increases early clearance of M. tuberculosis through induction of trained immunity. Epigenetic or metabolic modulation may further boost BCG-induced trained innate immunity to promote tuberculosis prevention. New tuberculosis vaccine candidates should also be examined for their capacity to improve protection against M. tuberculosis infection and induce trained immunity.

Evidence for supercoughers in an analysis of six tuberculosis cohorts from China, Peru, The Gambia and Uganda.

BACKGROUND: It is very difficult to observe tuberculosis (TB) transmission chains and thus, identify superspreaders. We investigate cough duration as a proxy measure of transmission to assess the presence of potential TB superspreaders.DESIGN: We analyzed six studies from China, Peru, The Gambia and Uganda, and determined the distribution of cough duration and compared it with several theoretical distributions. To determine factors associated with cough duration, we used linear regression and boosted regression trees to examine the predictive power of patient, clinical and environmental characteristics.RESULTS: We found within-study heterogeneity in cough duration and strong similarities across studies. Approximately 20% of patients contributed 50% of total cough days, and around 50% of patients contributed 80% of total cough days. The cough duration distribution suggested an initially increasing, and subsequently, decreasing hazard of diagnosis. While some of the exposure variables showed statistically significant associations with cough duration, none of them had a strong effect. Multivariate analyses of different model types did not produce a model that had good predictive power.CONCLUSION: We found consistent evidence for the presence of supercoughers, but no characteristics predictive of such individuals.

Point of care HbA1c level for diabetes mellitus management and its accuracy among tuberculosis patients: a study in four countries.

BACKGROUND: Diabetes mellitus (DM) is common among tuberculosis (TB) patients and often undiagnosed or poorly controlled. We compared point of care (POC) with laboratory glycated haemoglobin (HbA1c) testing among newly diagnosed TB patients to assess POC test accuracy, safety and acceptability in settings in which immediate access to DM services may be difficult. METHODS: We measured POC and accredited laboratory HbA1c (using high-performance liquid chromatography) in 1942 TB patients aged 18 years recruited from Peru, Romania, Indonesia and South Africa. We calculated overall agreement and individual variation (mean ± 2 standard deviations) stratified by country, age, sex, body mass index (BMI), HbA1c level and comorbidities (anaemia, human immunodeficiency virus [HIV]). We used an error grid approach to identify disagreement that could raise significant concerns. RESULTS: Overall mean POC HbA1c values were modestly higher than laboratory HbA1c levels by 0.1% units (95%CI 0.1-0.2); however, there was a substantial discrepancy for those with severe anaemia (1.1% HbA1c, 95%CI 0.7-1.5). For 89.6% of 1942 patients, both values indicated the same DM status (no DM, HbA1c <6.5%) or had acceptable deviation (relative difference <6%). Individual agreement was variable, with POC values up to 1.8% units higher or 1.6% lower. For a minority, use of POC HbA1c alone could result in error leading to potential overtreatment (n = 40, 2.1%) or undertreatment (n = 1, 0.1%). The remainder had moderate disagreement, which was less likely to influence clinical decisions. CONCLUSION: POC HbA1c is pragmatic and sufficiently accurate to screen for hyperglycaemia and DM risk among TB patients.

Clinical management of combined tuberculosis and diabetes.

Optimal management of combined tuberculosis (TB) and diabetes (DM) is important but challenging in terms of achieving good disease outcomes and avoiding toxicity, drug interactions and other challenges. DM management during anti-tuberculosis treatment, aimed at improving TB treatment outcomes and reducing DM-related morbidity and mortality, consists of glycaemic control and measures to reduce the risk of cardiovascular disease. Metformin, the glucose-lowering drug of choice for TB patients, has no meaningful interaction with rifampicin (RMP), and may reduce TB mortality. Insulin is effective for severe hyperglycaemia, but has several disadvantages that limit its use in TB patients. Cardiovascular risk assessment should be considered in TB-DM patients to guide management in terms of counselling and prescription of antihypertensive, lipid-lowering and anti-platelet treatment. With regard to anti-tuberculosis treatment, DM is associated with an increased risk of drug resistance, lower exposure to anti-tuberculosis drugs, treatment failure and recurrent TB. Patients therefore need careful assessment before, during and possibly after anti-tuberculosis treatment. Although no studies have been performed, anti-tuberculosis treatment may also have to be prolonged or intensified in terms of regimen or drug dosage if DM is present. With regard to service delivery, combined treatment should probably be administered, supervised and monitored as much as possible in a TB clinic. Local circumstances and severity of DM will guide the need for referral of patients to specialised DM care, and continuation of DM care after completion of anti-tuberculosis treatment. More data are also needed for the management of TB-DM patients with human immunodeficiency virus co-infection.

Computer-assisted chest radiography reading for tuberculosis screening in people living with diabetes mellitus.

BACKGROUND: Diabetes mellitus is a significant risk factor for tuberculosis (TB). We evaluated the performance of computer-aided detection for tuberculosis (CAD4TB) in people living with diabetes mellitus (PLWD) in Indonesia. METHODS: PLWD underwent symptom screening and chest X-ray (CXR); sputum was examined in those with positive symptoms and/or CXR. Digital CXRs were scored using CAD4TB and analysed retrospectively using clinical and microbiological diagnosis as a reference. The area under the receiver operator curve (AUC) of CAD4TB scores was determined, and an optimal threshold score established. Agreement between CAD4TB and the radiologist's reading was determined. RESULTS: Among 346 included PLWD, seven (2.0%) had microbiologically confirmed and two (0.6%) had clinically diagnosed TB. The highest agreement of CAD4TB with radiologist reading was achieved using a threshold score of 70 (κ = 0.41, P < 0.001). The AUC for CAD4TB was 0.89 (95%CI 0.73-1.00). A threshold score of 65 for CAD4TB resulted in a sensitivity, specificity, positive predictive value and negative predictive value of respectively 88.9% (95%CI 51.8-99.7), 88.5% (95%CI 84.6-91.7), 17.0% (95%CI 7.6-30.8) and 99.6% (95%CI 98.2-100). With this threshold, 48 (13.9%) individuals needed microbiological examination and no microbiologically confirmed cases were missed. CONCLUSIONS: CAD4TB has potential as a triage tool for TB screening in PLWD, thereby significantly reducing the need for microbiological examination.

Rising ELISPOT count prior to the onset of symptoms of full-blown tuberculosis disease.

The relationship between the T-cell response to mycobacterial antigens and the likelihood of progression to disease has not been defined. We report a rapidly rising ELISPOT count in a 55-year-old man with evidence of Mycobacterium tuberculosis infection prior to the onset of symptoms of disease. This case illustrates the possible utility of quantitative changes in the ELISPOT count in predicting progression from M. tuberculosis infection to disease.

Clinical presentation and outcome of tuberculosis patients infected by M. africanum versus M. tuberculosis.

SETTING: A tuberculosis (TB) case contact study in the Gambia. OBJECTIVE: To test whether Mycobacterium africanum, which has lost around 68 kb compared with M. tuberculosis sensu stricto, causes less severe TB disease. DESIGN: We genotyped mycobacterial isolates and compared clinical and radiological characteristics as well as outcome data of M. africanum-infected TB patients with those infected with M. tuberculosis. RESULTS: Of 317 index cases, 301 had a mycobacterial isolate available, 290 of which had an interpretable spoligotype pattern. Of these, 110 isolates (38%) were M. africanum and 180 (62%) were M. tuberculosis. M. africanum cases had lower body mass indices (17 vs. 17.45 for M. tuberculosis-infected patients, P = 0.029) and their radiographic disease was more extensive (96% vs. 89% had at least moderately severe radiographic changes, P = 0.031). Outcome on treatment was similar (2.8% of human immunodeficiency virus [HIV] negative M. africanum patients died on treatment vs. 3.0% of M. tuberculosis patients, P = 0.95). CONCLUSION: M. africanum causes sputum smear-positive tuberculosis disease that is at least as severe as that caused by M. tuberculosis sensu stricto. Further clinical comparisons may be helpful in smear-negative patients and HIV-TB co-infected patients, and to identify whether there is any difference in time to develop disease.