Introduction of the Simple One-Step stool Xpert Ultra method to detect TB in children and adults.

SETTING: In 2020, the National TB Programme (NTP) of Vietnam conducted an implementation pilot of the Simple One-Step (SOS) stool processing method using Xpert® MTB/RIF Ultra (Ultra) among children and people living with HIV (PLHIV) with signs and symptoms of TB.DESIGN and OBJECTIVES: Using data from this pilot and collecting information on healthcare workers´ (HCWs) perceptions, we assessed the feasibility, acceptability and potential impact of routine stool testing for TB.RESULTS: HCWs perceived collection of stools from children as least stressful of all sample types, stool processing as acceptable and the SOS stool method as easy to perform. After a 3-month induction period, the proportion of initial non-determinate Ultra stool tests was less than 5%. Combined Ultra testing of a respiratory sample and stool resulted in an increase in the proportion of bacteriologically confirmed TB among PLHIV and children by respectively 4.1% (95% CI 1.6-6.6) and 3.9% (95% CI 1.6-6.2). Among children, Mycobacterium tuberculosis was more often detected in stool (26.1%) than in respiratory samples (23.4%) (P = 0.06), including one child with rifampicin resistance.CONCLUSION: Stool testing can be feasibly implemented both in adult PLHIV and in children in routine settings, providing a non-invasive alternative sample type for the diagnosis of TB for patients who cannot produce sputum.

Acceptability, feasibility, and likelihood of stakeholders implementing the novel BPaL regimen to treat extensively drug-resistant tuberculosis patients.

BACKGROUND: BPaL, a 6 month oral regimen composed of bedaquiline, pretomanid, and linezolid for treating extensively drug-resistant tuberculosis (XDR-TB) is a potential alternative for at least 20 months of individualized treatment regimens (ITR). The ITR has low tolerability, treatment adherence, and success rates, and hence to limit patient burden, loss to follow-up and the emergence of resistance it is essential to implement new DR-TB regimens. The objective of this study was to assess the acceptability, feasibility, and likelihood of implementing BPaL in Indonesia, Kyrgyzstan, and Nigeria. METHODS: We conducted a concurrent mixed-methods study among a cross-section of health care workers, programmatic and laboratory stakeholders between May 2018 and May 2019. We conducted semi-structured interviews and focus group discussions to assess perceptions on acceptability and feasibility of implementing BPaL. We determined the proportions of a recoded 3-point Likert scale (acceptable; neutral; unacceptable), as well as the overall likelihood of implementing BPaL (likely; neutral; unlikely) that participants graded per regimen, pre-defined aspect and country. We analysed the qualitative results using a deductive framework analysis. RESULTS: In total 188 stakeholders participated in this study: 63 from Kyrgyzstan, 51 from Indonesia, and 74 from Nigeria The majority were health care workers (110). Overall, 88% (146/166) of the stakeholders would likely implement BPaL once available. Overall acceptability for BPaL was high, especially patient friendliness was often rated as acceptable (93%, 124/133). In contrast, patient friendliness of the ITR was rated as acceptable by 45%. Stakeholders appreciated that BPaL would reduce workload and financial burden on the health care system. However, several stakeholders expressed concerns regarding BPaL safety (monitoring), long-term efficacy, and national regulatory requirements regarding introduction of the regimen. Stakeholders stressed the importance of addressing current health systems constraints as well, especially in treatment and safety monitoring systems. CONCLUSIONS: Acceptability and feasibility of the BPaL regimen is high among TB stakeholders in Indonesia, Kyrgyzstan, and Nigeria. The majority is willing to start using BPaL as the standard of care for eligible patients despite country-specific health system constraints.

Introducing bedaquiline: experiences from the Challenge TB Project.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) remains a global public health crisis. In 2013, the World Health Organization recommended the introduction of bedaquiline (BDQ) for eligible DR-TB patients.METHODS: We conducted a retrospective review and analyses of project reports from 2016 to mid-2019 on the processes, activities implemented, available results on enrolment and interim treatment outcomes, across the 23 Challenge TB (CTB) supported countries.RESULTS: Initial introduction of BDQ-containing regimens in the 23 CTB-supported countries took on average 2 years, with subsequent nation-wide scale-up achieved in Ethiopia and Kyrgyzstan within a short time period. Successful implementation required critical interventions including advocacy, revision of policies and guidelines, capacity building of health care workers, and strengthening of laboratory networks. The number of countries providing BDQ increased from 9 to 23; 9398 patients were enrolled on bedaquiline containing regimens; 71% were culture-negative after 6 months of treatment; and the number of countries reporting serious adverse events increased (from 5 to 18). Major challenges included limited in-country coordination with drug regulatory agencies, unrealistic quantification and drug ordering, weak laboratory networks and reporting systems for drug safety.CONCLUSION: BDQ introduction required a systematic and programmatic approach. The initial time investment helped achieve initial introduction and scale-up of coverage, ownership and sustainability by National TB Programmes.

Estimation of subnational tuberculosis burden: generation and application of a new tool in Indonesia.

SETTING: In many high tuberculosis (TB) burden countries, there is substantial geographical heterogeneity in TB burden. In addition, decisions on TB funding and policy are highly decentralised. Subnational estimates of burden, however, are usually unavailable for planning and target setting.OBJECTIVE and DESIGN: We developed a statistical model termed SUBsET to estimate the distribution of the national TB incidence through a weighted score using selected variables, and applied the model to the 514 districts in Indonesia, which have substantial policy and budgetary autonomy in TB. Estimated incidence was compared to reported facility and domicile-based notifications to estimate the case detection rate (CDR). Local stakeholders led model development and dissemination.RESULTS: The final SUBsET model included district population size, level of urbanisation, socio-economic indicators (living floor space and high school completion), human immunodeficiency virus prevalence and air pollution. We estimated district-level TB incidence to be between 201 and 2,485/100 000/year. The facility-based CDR varied between 0 and 190%, with high variation between neighbouring districts, suggesting strong cross-district health utilisation, which was confirmed by domicile-based CDR estimation. SUBsET results informed district-level TB action plans across Indonesia.CONCLUSION: The SUBsET model could be used to estimate the subnational burden in high-burden countries and inform TB policymaking at the relevant decentralised administrative level.

WHO guidelines for the programmatic management of drug-resistant tuberculosis: 2011 update.

The production of guidelines for the management of drug-resistant tuberculosis (TB) fits the mandate of the World Health Organization (WHO) to support countries in the reinforcement of patient care. WHO commissioned external reviews to summarise evidence on priority questions regarding case-finding, treatment regimens for multidrug-resistant TB (MDR-TB), monitoring the response to MDR-TB treatment, and models of care. A multidisciplinary expert panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to develop recommendations. The recommendations support the wider use of rapid drug susceptibility testing for isoniazid and rifampicin or rifampicin alone using molecular techniques. Monitoring by sputum culture is important for early detection of failure during treatment. Regimens lasting ≥ 20 months and containing pyrazinamide, a fluoroquinolone, a second-line injectable drug, ethionamide (or prothionamide), and either cycloserine or p-aminosalicylic acid are recommended. The guidelines promote the early use of antiretroviral agents for TB patients with HIV on second-line drug regimens. Systems that primarily employ ambulatory models of care are recommended over others based mainly on hospitalisation. Scientific and medical associations should promote the recommendations among practitioners and public health decision makers involved in MDR-TB care. Controlled trials are needed to improve the quality of existing evidence, particularly on the optimal composition and duration of MDR-TB treatment regimens.

Household expenditure and tuberculosis prevalence in VietNam: prediction by a set of household indicators.

OBJECTIVE: To study the association between TB and household expenditure in a nationwide TB prevalence survey in Viet Nam using nine household characteristics. METHOD: To assess the prevalence of TB in Viet Nam, a nationwide stratified cluster sample survey was conducted from 2006 to 2007. Nine household characteristics used in the second Viet Nam Living Standards Survey (VLSS) were scored per household. In the VLSS dataset, we regressed these nine characteristics against household expenditure per capita, and used the coefficients to predict household expenditure level (in quintiles) in our survey and assess its relation with TB prevalence. RESULTS: The prevalence of bacteriologically confirmed TB was 307 per 100,000 population in persons aged ≥ 15 years (95%CI 249-366). After adjustment for confounders, prevalence was found to be associated with household expenditure level: the rate was 2.5 times higher for those in the lowest household expenditure quintile (95%CI 1.6-3.9) than those in the highest quintile. CONCLUSION: With a set of nine household characteristics, we were able to predict household expenditure level fairly accurately. There was a significant association between TB prevalence rates and estimated household expenditure level, showing that TB is related to poverty in Viet Nam.

Predictive value for progression to tuberculosis by IGRA and TST in immigrant contacts.

The authors determined the positive predictive value (PPV) for progression to tuberculosis (TB) of two interferon-gamma release assays (IGRAs), QuantiFERON-TB Gold In-tube (QFT-GIT) and T-SPOT.TB, and the tuberculin skin test (TST) in immigrants contacts. Immigrant close contacts of sputum smear-positive TB patients were included when aged > or =16 yrs and their TST result was > or =5 mm 0 or 3 months after diagnosis of the index patient. Contacts were followed for the next 2 yrs for development of TB disease. Of 339 immigrant contacts with TST > or =5 mm, 324 and 299 had valid results of QFT-GIT and T-SPOT.TB, respectively. Nine contacts developed active TB. One patient had not been tested with TST, while another patient had not been tested with QFT-GIT and T-SPOT.TB. The PPV for progression to TB during this period was 9/288 = 3.1% (95% CI 1.3-5.0%) for TST > or =10 mm, 7/184 = 3.8% (95% CI 1.7-5.9%) for TST > or =15 mm, 5/178 = 2.8% (95% CI 1.0-4.6%) for QFT-GIT and 6/181 = 3.3% (95% CI 1.3-5.3%) for T-SPOT.TB. Sensitivity was 100%, 88%, 63% and 75%, respectively. The predictive values of QFT-GIT, T-SPOT.TB and TST for progression to TB disease among immigrant close contacts were comparable.

Genetic association of DLG5 R30Q with familial and sporadic inflammatory bowel disease in men.

BACKGROUND: The association of DLG5 R30Q with IBD has been replicated in several populations, but is not statistically significant in others. We studied the incidence of DLG5 alleles in a population of IBD patients from Pennsylvania. METHODS: DLG5 R30Q (rs1248696) and G1066G (rs1248634) were analyzed with PCR-based RFLP methods in a total of 521 subjects, that included 105 individuals with IBD and 139 without IBD from a familial IBD registry, 107 with sporadic IBD, and 170 unrelated healthy controls. R30Q was further analyzed with SNPlex Genotyping System in 473 samples. RESULTS: RFLP genotyping data showed that, DLG5 R30Q was significantly associated with IBD overall (p=0.006), and separately with CD (p=0.009) and UC (p=0.024). The association of R30Q with IBD was entirely due to a male-associated effect (male vs female p=0.015 vs 0.241 (IBD), p=0.024 vs 0.190 (CD), and p=0.019 vs 0.575 (UC)). The frequency of the A allele carriage was elevated in both affected and unaffected members in the familial IBD cohort compared to healthy controls (p=0.037). In the family pedigrees, we observed differences in the expression of IBD in individuals carrying the A allele between families. CONCLUSIONS: In the studied population, DLG5 R30Q was associated with all forms of IBD. An elevated presence of the R30Q variant was observed in all members of a familial IBD registry. This association of the R30Q variant with IBD was male-specific.

Liquid culture for Mycobacterium tuberculosis: proceed, but with caution.

Attempts to improve the diagnosis of tuberculosis (TB) in high-burden countries has resulted in significant funding and initiatives to change the method of diagnosis of TB from light microscopy supplemented with X-ray to a sophisticated diagnostic algorithm based on the latest technological innovations. Such activities are overdue and should be welcomed, but the lack of skills and support available to interpret and use the results represents a danger. The introduction of new diagnostic methods, particularly liquid culture, should be carefully structured according to the local situation, failing which frustration and the disruption of previously underdeveloped but adequately functioning laboratories may result.

EuroSCORE as a predictor for complications and outcome.

OBJECTIVE: The purpose of this study was to evaluate the usefulness of EuroSCORE in terms of prediction of the outcome as a result of preoperative information in a cohort of patients. METHODS: We analyzed the data from 751 patients treated between Jan 1 and Dec 31, 1998. We used contingency tables and applied methods of discriminant analysis for the evaluation. RESULTS: Compared to the 14.799 patients from whose data the EuroSCORE system had originally been derived [1,2], we had a smaller portion of patients in the low-risk group (24.5% vs. 30.6%), a comparable portion of patients in the medium-risk group (42.2% vs. 40.5%) and a higher proportion of patients in the high-risk group (33.2% vs. 29.0%). This difference in the risk distributions was highly significant (p < 0.001). The application of the EuroSCORE system showed that deaths only occurred in the high-risk group in our hospital. We had 36 deaths amongst the patients, which gives an overall mortality rate of 4.9% and a mortality rate of 1.6% in the medium-risk group and of 12.4% in the high-risk group. The discriminant analysis showed that with the EuroSCORE as single predicting variable - virtually all survivors were classified correctly (giving a specificity of 99.0%). The sensitivity was rather low at only 25%; however, this means that many of the high-risk patients in our clinic survived. The total misclassification rate, however, was 12.7%. Additionally, we found that a higher score value predicts a significantly higher probability for perioperative complications and also results in significantly increased average times for the bypass and total time for surgery. CONCLUSION: The EuroSCORE is a valuable score system for the prediction of the overall outcome of patients following open heart surgery, and is easy to use. As far as perioperative complications are concerned, however, some specifications seem desirable.

[Image analysis system for detection facial paralysis]. / Bildanalysesystem zur Erkennung einer Fazialisparese.

BACKGROUND: Evaluation of facial nerve paresis depends on visual assessment and naturally differs from examiner to examiner. An objective measurement instrument is presented. PATIENTS AND METHOD: Facial features are automatically localized by a parametric face model in videos of a face during relaxation and exercises. Gray-level information is analyzed by a special steerable filter and used to identify symmetries. The computer system was tested in 19 individuals. RESULTS: Automatic localization of facial features such as the upper arc of the head and ears was correct in 95%, the eyes in 82%, and the mouth in 73%. Lid paresis was correctly recognized in seven of ten (70%) and oral paresis in 10 of 12 (83%) cases. Unaffected eyelid movements were identified in eight of nine (89%) and healthy oral regions in all seven (100%) cases. CONCLUSION: The computer system presented is able to automatically localize facial features and to identify facial nerve paresis. It is a considerable step toward automatic and objective grading of facial nerve paresis.

The apical membrane of intestinal brush cells possesses a specialised, but species-specific, composition of glycoconjugates--on-section and in vivo lectin labelling in rats, guinea-pigs and mice.

Brush cells are specialised epithelial cells that are assumed to represent chemoreceptors of the digestive tract. They comprise a small population of the epithelial cells lining the intestine, possess a unique ultrastructure and, in many aspects, resemble the receptor cells of taste buds. To characterise glycoconjugates possibly involved in a sensory function, we investigated brush cells in the small intestine of three species using lectin histochemistry in confocal light and thin-section electron microscopy. Brush cells of rats were selectively labelled by the sialic acid-specific lectin Maackia amurensis agglutinin, those of guinea-pigs by the D-galactose-specific lectin Bandeiraea simplicifolia agglutinin, isolectin B4 and those of mice by the L-fucose-specific lectin Ulex europaeus agglutinin lectin I. Lectin binding sites were consistently located in the glycocalyx of the apical membrane and in that of cytoplasmic vesicles. In vivo lectin labelling revealed that the glycoconjugates of the apical membrane are accessible under physiological conditions, that brush cells do not endocytose and that they probably possess a high membrane turnover rate. The results show that specialisations exist in the composition of glycoconjugates forming the glycocalyx of brush cells in all species investigated. The presence of brush cell-specific glycoconjugates would be in accordance with the current hypothesis of a receptive function of brush cells. Differences in the specific glycosylation patterns among rats, guinea-pigs and mice indicate that species-specific adaptations exist.

Brush cells of the mouse intestine possess a specialized glycocalyx as revealed by quantitative lectin histochemistry. Further evidence for a sensory function.

Brush cells occur in the epithelium of the small intestine and in various other epithelia of endodermal origin. Ultrastructural and histochemical characteristics suggest that they represent sensory cells. Because the apical membrane of brush cells might be involved in and specialized for (chemo-)receptive functions, we investigated the composition of the glycocalyx and compared it with that of enterocytes. Ultrathin sections of murine small intestine were labeled with a panel of eight lectins. Their binding sites in the brush border and on vesicles of the apical cytoplasm were detected by colloidal gold and quantified using image analysis. The glycocalyx of brush cells contained significantly higher amounts of l-fucose residues than that of enterocytes, as detected by the lectins UEA-I and LTA. In contrast, most of the other lectins bound more avidly to the glycocalyx of enterocytes. The cytoplasmic vesicles closely resembled the apical membrane in their labeling pattern. Quantitation of the brush cells' distribution revealed that the epithelia of the Peyer's patches contained 10-fold higher numbers of brush cells than the small intestinal mucosa distant from lymphoid tissue. We conclude that brush cells possess a glycocalyx with a specialized composition and differ significantly from enterocytes. Because similar peculiarities of the apical membrane have previously been described for sensory cells of the olfactory and gustatory organs, this study provides further evidence in favor of a sensory function of brush cells.

Interrater reliability of the Peabody Developmental Motor Scales: fine motor scale.

OBJECTIVE: The interrater reliability of the Peabody Developmental Motor Scales (PDMS) fine motor scale was examined in 23 children with developmental disabilities who were between 2 years and 5 years of age. METHOD: Three occupational therapists viewed videotapes of the children and scored each child's performance on the fine motor section of the test. Data were analyzed with the intraclass correlation (ICC) approach; ICC values ranged from 0.90 to 0.97 for the subskills of Grasping, Hand Use, Eye-Hand Coordination, and Manual Dexterity. RESULTS: The ICC interrater reliability value for the total fine motor score was 0.99. Reliability values were additionally computed with the PDMS fine motor scale age-equivalent scores and Z scores. The ICC values for these methods of scoring the PDMS were 0.99 and 1.00, respectively. CONCLUSION: The PDMS fine motor scale can be used consistently to evaluate fine motor delays in this population of young children.

Result of treatment in children with tuberculosis. Evaluation of indications for and results of treatment in a 5 years cohort of children treated for tuberculosis in Turiani Hospital Tanzania.

Between January 1983 and January 1988 a total of 146 children started tuberculosis (TB) treatment in Turiani Hospital, Tanzania. During the treatment period 16 children died and another 16 were transferred out. From the remaining 114 children, 84 could be traced and were visited at home. Out of this group 85% were found to be in good clinical condition, whereas 7% had a moderate condition and 1% were seriously ill. Tuberculin sensitivity testing has been carried out in 53 children from the follow-up group. The indications for treatment and the results of the follow-up study are discussed.

Tuberculosis in children: treatment evaluation and results in a 5 year cohort of children with tuberculosis in Turiani Hospital, Tanzania.

Between January 1983 and January 1988, a total of 146 children started TB treatment in Turiani Hospital, Tanzania. During the treatment period 16 children died and another 16 have been transferred out. From the remaining 114, 84 could be traced and were visited at home. Out of this group, 85% were found to be in good clinical condition, and 1% was in bad shape. Death had occurred in 7% after finishing their treatment. Medical records of all children were analysed. Tuberculin sensitivity testing has been carried out in 53 children from the follow-up group. The indications for treatment and the results of the follow-up study are discussed.

PIP: Physicians began tuberculosis (TB) treatment on 146 children at Turiani Hospital in the Morogoro North district, Tanzania between January 1983-January 1988. 46% were 2 years old and 9% were 12 years old. Treatment consisted of daily doses of 20 mg/kg streptomycin and 15 mg/kg thiazina for the 8 week hospital stay followed by the same dose of thiazina for 10 months. Some cases also received rifampicin and pyrazinamide. They administered tubercullin sensitivity tests to 53 of the 84 children who could be traced and visited. Researchers followed the TB case to evaluate indications for and the results of TB treatment in children. The physicians began treatment in some case even though the cases did not exhibit clear symptoms of TB. 74% of the patients whose BCG status was recorded had earlier received a BCG vaccination. Research showed that BCG vaccination protects against 2 severe forms of TB, meningeal and milliary, both of which were not present in this population. At the end of 5 years, 7% (6) of the patients died and only 1% (1) was in poor condition. 85% of all follow up patients were in good condition and well nourished. Even most of the patients who ended treatment rather early after leaving the hospital (74%) were well. In fact, no significant difference in the condition between defaulters and patients who completed treatment existed. This showed that a shorter duration of treatment may be as effective as 10 months of treatment. Only 34% of tested children reacted to the tuberculin sensitivity test which could mean that physicians overtreated around 60% of the patients. 25% of the children who had a negative reaction had abcesses while none of those with a positive reaction had abcesses. In conclusion, physicians should administer a tuberculin sensitivity test at the end of the 8 weeks of treatment to prevent overtreatment.