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BACKGROUND: In Nigeria, most children with tuberculosis (TB) present at primary health clinics where there are limited personnel skilled in collecting appropriate respiratory specimens from those who cannot produce sputum. KNCV Nigeria, in collaboration with the National Tuberculosis Control Program, implemented a modified simple, one-step (SOS), stool-based Xpert MTB/RIF method for diagnosis of TB in children who cannot expectorate sputum. We evaluated the impact of its implementation on childhood TB diagnosis. METHOD: A cross-sectional study was conducted across 14 selected states using secondary data of children presumed to have TB. Stool was collected from children presumed to have TB and processed using Xpert. RESULT: Out of 52,117 presumptive TB cases, 52% were male and 59.7% were under 5 years old. A total of 2440 (5%) cases were diagnosed with TB, and 2307 (95%) were placed on treatment. Annual TB notifications increased significantly after the introduction of the stool-based Xpert test when compared to those in the pre-implementation period. Increasing contributions from stool testing were observed throughout the implementation period, except in 2020 during the COVID-19 era. Overall, stool Xpert testing improved childhood TB notification in the studied states. Interventions aimed at awareness creation, capacity building, and active case finding improved the performance of the test.
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One quarter of the world's population is estimated to be infected with Mycobacterium tuberculosis. Identifying recent TB infection (TBI) offers an avenue to targeted TB preventative therapy provision, and prevention to disease progression. However, detecting recent TBI remains challenging. The QuantiFERON-TB Gold Plus assay (QFT-Plus) claims to have improved sensitivity in detecting recent TBI, by the addition of the TB2 antigen tube to the TB1 tube used in previous tests. TB2 detects CD8-mediated interferon gamma response, a potential marker of recent infection. We compared QFT-Plus TB1 and TB2 responses in individuals with recent and remote infection in high-burden settings. The Tuberculosis Reduction through Expanded Antiretroviral Treatment and TB Screening (TREATS) Project followed a cohort of adolescents and young people (AYP) aged 15-24 years in Zambia and South Africa to determine TBI incidence measured by QFT-Plus over 24 months. We categorised individuals with QTF-Plus positive result into recent and remote infection. We compared their TB1 and TB2 responses and the antigen tube differential [TB2-TB1], an indicator of CD8-activity, using logistic regression. At baseline, 3876 AYP, 1852/3876 (47.8%) were QFT-Plus positive whilst 2024/3876 (52.2%) QFT-Plus negative. Of the QFT-Plus baseline positives, 1069/1852 (57.7%) tested positive at both 12 and 24 months-remote infection. Of the QFT-Plus baseline negatives, 274/2024(13.3%) converted within a 12-month period- recent infection. TB1 and TB2 responses were higher in remote than recent infection. In recent infection, TB2 responses were greater than TB1 responses. The mean differential was 0.01 IU/ml in recent and -0.22 IU/ml in remote infection, (p = 0.145). The quantitative QFT-Plus results did not appear to reflect a marked distinction between recent and remote infection. Further analysis of the responses of infected individuals who developed disease is required to determine whether any signal in QFT-Plus results may predict progression to disease.
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Background: Childhood tuberculosis (TB) diagnosis remains challenging, partly because children cannot provide sputum. This study evaluated the diagnostic accuracy of the Simple One-Step (SOS) stool method with Xpert MTB/RIF Ultra (Xpert-Ultra) for childhood TB compared to culture and Xpert-Ultra on a respiratory sample (RS) and clinical diagnosis. It also assessed the feasibility and acceptability of stool testing according to laboratory staff, and caregivers' sample preference. Methods: We enrolled children (≤10â years) with presumptive pulmonary tuberculosis in Ethiopia. RS was tested using Xpert-Ultra and culture; stool samples were tested using the SOS stool method with Xpert-Ultra. Laboratory staff and caregivers' opinions were assessed using standardised questionnaires. Results: Of the 898 children enrolled, 792, 832 and 794 were included for assessing the diagnostic accuracy of SOS stool with Xpert-Ultra against culture, RS Xpert-Ultra and clinical diagnosis, respectively, yielding sensitivity estimates for SOS stool with Xpert-Ultra of 69.1% (95% confidence interval (CI) 56.0-79.7%), 76.8% (95% CI 64.2-85.9%) and 59.0% (95% CI 47.9-69.2%), respectively. The specificity was ≥98.8% for all comparisons. The rate of non-determinate test results was 2.8% after one repeat test. According to laboratory staff, stool collection was feasible and acceptable and the SOS stool method was easy to perform. Most caregivers (75%) preferred stool for TB diagnosis over RS. Conclusion: This study shows that SOS stool Xpert-Ultra testing offers a good alternative to RS testing for TB in children who cannot spontaneously produce a sputum sample and would otherwise need to undergo invasive procedures to obtain RS for diagnosis.
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BACKGROUND: Tuberculosis (TB) prevalence remains persistently high in many settings, with new or expanded interventions required to achieve substantial reductions. The HIV Prevention Trials Network (HPTN) 071 (PopART) community-randomised trial randomised 14 communities to receive the "PopART" intervention during 2014 to 2017 (7 arm A and 7 arm B communities) and 7 communities to receive standard-of-care (arm C). The intervention was delivered door-to-door by community HIV care providers (CHiPs) and included universal HIV testing, facilitated linkage to HIV care at government health clinics, and systematic TB symptom screening. The Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening (TREATS) study aimed to measure the impact of delivering the PopART intervention on TB outcomes, in communities with high HIV and TB prevalence. METHODS AND FINDINGS: The study population of the HPTN 071 (PopART) trial included individuals aged ≥15 years living in 21 urban and peri-urban communities in Zambia and South Africa, with a total population of approximately 1 million and an adult HIV prevalence of around 15% at the time of the trial. Two sputum samples for TB testing were provided to CHiPs by individuals who reported ≥1 TB suggestive symptom (a cough for ≥2 weeks, unintentional weight loss ≥1.5 kg in the last month, or current night sweats) or that a household member was currently on TB treatment. Antiretroviral therapy (ART) was offered universally at clinics in arm A and according to local guidelines in arms B and C. The TREATS study was conducted in the same 21 communities as the HPTN 071 (PopART) trial between 2017 and 2022, and TB prevalence was a co-primary endpoint of the TREATS study. The primary comparison was between the PopART intervention (arms A and B combined) and the standard-of-care (arm C). During 2019 to 2021, a TB prevalence survey was conducted among randomly selected individuals aged ≥15 years (approximately 1,750 per community in arms A and B, approximately 3,500 in arm C). Participants were screened on TB symptoms and chest X-ray, with diagnostic testing using Xpert-Ultra followed by culture for individuals who screened positive. Sputum eligibility was determined by the presence of a cough for ≥2 weeks, or ≥2 of 5 "TB suggestive" symptoms (cough, weight loss for ≥4 weeks, night sweats, chest pain, and fever for ≥2 weeks), or chest X-ray CAD4TBv5 score ≥50, or no available X-ray results. TB prevalence was compared between trial arms using standard methods for cluster-randomised trials, with adjustment for age, sex, and HIV status, and multiple imputation was used for missing data on prevalent TB. Among 83,092 individuals who were eligible for the survey, 49,556 (59.6%) participated, 8,083 (16.3%) screened positive, 90.8% (7,336/8,083) provided 2 sputum samples for Xpert-Ultra testing, and 308 (4.2%) required culture confirmation. Overall, estimated TB prevalence was 0.92% (457/49,556). The geometric means of 7 community-level prevalence estimates were 0.91%, 0.70%, and 0.69% in arms A, B, and C, respectively, with no evidence of a difference comparing arms A and B combined with arm C (adjusted prevalence ratio 1.14, 95% confidence interval, CI [0.67, 1.95], p = 0.60). TB prevalence was higher among people living with HIV than HIV-negative individuals, with an age-sex-community adjusted odds ratio of 2.29 [95% CI 1.54, 3.41] in Zambian communities and 1.61 [95% CI 1.13, 2.30] in South African communities. The primary limitations are that the study was powered to detect only large reductions in TB prevalence in the intervention arm compared with standard-of-care, and the between-community variation in TB prevalence was larger than anticipated. CONCLUSIONS: There was no evidence that the PopART intervention reduced TB prevalence. Systematic screening for TB that is based on symptom screening alone may not be sufficient to achieve a large reduction in TB prevalence over a period of several years. Including chest X-ray screening alongside TB symptom screening could substantially increase the sensitivity of systematic screening for TB. TRIAL REGISTRATION: The TREATS study was registered with ClinicalTrials.gov Identifier: NCT03739736 on November 14, 2018. The HPTN 071 (PopART) trial was registered at ClinicalTrials.gov under number NCT01900977 on July 17, 2013.
Subject(s)
HIV Infections , HIV , Adult , Humans , South Africa/epidemiology , Zambia/epidemiology , Cross-Sectional Studies , Cough , Prevalence , HIV Infections/diagnosis , HIV Infections/drug therapy , HIV Infections/epidemiology , Research DesignABSTRACT
BACKGROUND: From 2018-2021 the TB Reduction through Expanded Antiretroviral Treatment and TB Screening (TREATS) project took place in 21 Zambian and South African communities. The TREATS Incidence of TB Infection Cohort Study was conducted in adolescents and young people (AYP), aged 15-24 years in 14 communities. We describe the baseline prevalence and risk factors of Mycobacterium tuberculosis (M. tuberculosis) infection among this cohort and explore the quantitative QFT-Plus interferon gamma (IFN-γ) responses. METHODS AND FINDINGS: A random sample of approximately 300 AYP per community were recruited and information on TB/HIV risk factors, TB symptoms and social mixing patterns collected. QuantiFERON TB Gold Plus assay (QFT-Plus) was used to detect M. tuberculosis infection, following manufacturer's instructions. Logistic regression was used to determine factors associated with infection. 5577 eligible AYP were invited to participate across both countries, with 4648 enrolled. QFT-Plus results were available for 4529: 2552(Zambia) and 1977(South Africa). Overall, 47.6% (2156/4529) AYP had positive QFT-Plus results, the prevalence of infection in South Africa being twice that in Zambia (64.7% (1280/1977) vs 34.3% (867/2552) p<0.001). Infection was associated with age, household contact with TB and alcohol in Zambia but showed no associations in South Africa. The antigen tube differential (TB2-TB1>0.6 IU/ml) of the assay at baseline showed no evidence of association with recent TB exposure. CONCLUSION: The high prevalence of infection in AYP warrants urgent action to address TB control, especially in South Africa. Further research is required to delineate antigen tube responses of the QFT-Plus assay more precisely to fully realise the benefit of the additional TB2 tube in high TB/HIV burden settings.
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The introduction of stool as a readily obtainable sample and the recently developed simple one-step (SOS) stool processing method on Xpert MTB/RIF Ultra (Xpert Ultra) offer an opportunity for TB diagnosis in children. We conducted this study in secondary health facilities in Ethiopia, which are the first-level referral facilities for childhood TB diagnosis and treatment, with the aim to determine if stool-based TB diagnosis can be performed with a reasonable level of concordance with sputum tests using Xpert MTB/RIF Ultra. Eligible children 0-14 years old with presumptive pulmonary TB were asked to provide stools in addition to routinely requested sputum samples. We determined the level of agreement between the stool and sputum test results. Of the 373 children included in the study, 61% were <5 years of age and 56% were male. Thirty-six children (9.7%) were diagnosed with TB, and all started treatment. The rate of concordance between stool and sputum was high, with a kappa value of 0.83 (p < 0.001). There were more Xpert Ultra positive results on stool (n = 27 (7.2%)) than on sputum/NGA (n = 23 (6.2%)). Laboratories in secondary hospitals can perform stool-based TB diagnosis in children, with high concordance between stool and sputum test results reaffirming the applicability of the SOS stool method.
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BACKGROUND: HPTN071 (PopART) was a cluster randomized trial conducted in Zambian and South African (SA) communities, between 2013-2018. The PopART intervention (universal HIV-testing and treatment (UTT) combined with population-level TB symptom screening) was implemented in 14 communities. The TREATS study (2017-2021) was conducted to evaluate the impact of the PopART intervention on TB outcomes. We report on the impact of the combined TB/HIV intervention on the incidence of TB infection in a cohort of adolescents and young adults (AYA) aged 15-24 years. METHODS: A random sample of AYA was enrolled between July 2018 and July 2019 in 7 intervention vs 7 standard-of-care communities. We collected questionnaire data on risk factors for TB, and blood for measuring TB infection using QuantiFERON (QFT) Plus. AYA were seen at months 12 and 24 with all procedures repeated. Primary outcome was incidence of TB infection comparing intervention and standard-of-care communities. An incident case was defined as a participant with QFT interferon-gamma response of < 0.2 IU/ml plasma ('negative') at baseline and a QFT interferon-gamma response of > = 0.7 IU/ml ('positive') at follow up. RESULTS: We enrolled 4,648 AYA, 2,223 (47.8%) had a negative QFT-plus result at baseline, 1,902 (85.6%) had a follow up blood sample taken at 12 months or 24 months. Among the 1,902 AYA, followed for 2,987 person-years, 213 had incident TB infection giving (7.1 per 100 person-years). TB infection incidence rates were 8.7 per 100 person-years in intervention communities compared to 6.0 per 100 person-years in standard-of-care communities. There was no evidence the intervention reduced the transmission of TB (incidence-rate-ratio of 1.45, 95%CI 0.97-2.15, p = 0.063). CONCLUSION: In our trial setting, we found no evidence that UTT combined with TB active case finding reduced the incidence of TB infection at population level. Our data will inform future modelling work to better understand the population level dynamics of HIV and TB.
ABSTRACT
Stool is recommended as an alternative specimen for the diagnosis of tuberculosis (TB) in young children, as they cannot easily produce sputum. The Simple One-Step (SOS) stool processing method is a new and simple stool processing method for the detection of Mycobacterium tuberculosis (MTB) using Xpert MTB/RIF Ultra (Xpert-Ultra). We determined the robustness of the SOS stool processing method and stool specimen transport conditions in participants with confirmed TB. We processed stool using the standard protocol after simulated "transport," varying time, and temperature, and experimented with slightly modified processing steps. We included 2,963 Xpert-Ultra test results from 132 stool specimens of 47 TB participants, including 11 children aged <10 years. We compared Xpert-Ultra processing errors and MTB positivity rates between standard and modified procedures. Minor deviations from the standard SOS protocol did not significantly impact the Xpert-Ultra test outcomes. The rate of Xpert-Ultra processing errors significantly increased with noncold-chain transport, exposure of stool to sample reagent at room temperature or beyond 12 h, and adding >0.8 g of stool. We found that almost all steps in the current SOS stool processing method provide optimal Xpert-Ultra results but recommend an adjustment to use a wider range of stool amounts (0.3 to 0.8 g) than advised previously (0.8 g). With this adaptation, stool-based diagnosis of TB using the SOS stool processing method can be scaled-up. IMPORTANCE The manuscript will support the global implementation and scale-up of the SOS stool method in routine settings. It also provides important insights on the optimal stool transport conditions and robustness of the SOS method, which can be used for bacteriological diagnosis of TB in children at the lowest levels of the healthcare system, avoiding lengthy healthcare-seeking pathways and additional costs.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Child , Humans , Child, Preschool , Tuberculosis, Pulmonary/microbiology , Sensitivity and Specificity , Tuberculosis/diagnosis , Tuberculosis/microbiology , Feces/microbiologyABSTRACT
BACKGROUND: WHO recommends community-wide, systematic tuberculosis screening in high-prevalence settings. C-reactive protein has been proposed as a tuberculosis screening tool for people living with HIV. We aimed to assess the performance of a point-of-care C-reactive protein test for tuberculosis screening in the community in two countries with a high tuberculosis burden. METHODS: We conducted a prospective, cross-sectional study in four communities in Zambia and South Africa, nested in a tuberculosis prevalence survey. We included adults (aged ≥15 years) who were sputum-eligible (tuberculosis-suggestive symptoms or computer-aided-detection score ≥40 on chest x-ray) and whose sputum was tested with Xpert Ultra and liquid culture. A 5% random sample of individuals who were non-sputum-eligible was also included. We calculated sensitivity and specificity of point-of-care C-reactive protein testing, alone and combined with symptom screening, to detect tuberculosis in participants who were sputum-eligible, compared with a microbiological reference standard (positive result in Xpert Ultra, culture, or both). FINDINGS: Between Feb 19 and Aug 11, 2019, 9588 participants were enrolled in the tuberculosis prevalence study, 1588 of whom had C-reactive protein testing and received results (875 [55·1%] were women and girls, 713 [44·9%] were men and boys, 1317 [82·9%] were sputum-eligible, and 271 [17·1%] were non-sputum-eligible). Among participants who were sputum-eligible, we identified 76 individuals with tuberculosis, of whom 25 were living with HIV. Sensitivity of point-of-care C-reactive protein testing with a cutoff point of 5 mg/L or more was 50·0% (38/76, 95% CI 38·3-61·7) and specificity was 72·3% (890/1231, 69·7-74·8). Point-of-care C-reactive protein combined in parallel with symptom screening had higher sensitivity than symptom screening alone (60·5% [46/76, 95% CI 48·6-71·6] vs 34·2% [26/76, 23·7-46·0]). Specificity of point-of-care C-reactive protein combined in parallel with symptom screening was 51·7% (636/1231, 95% CI 48·8-54·5) versus 70·5% (868/1231, 67·9-73·0) with symptom screening alone. Similarly, in people living with HIV, sensitivity of point-of-care C-reactive protein combined with symptom screening was 72·0% (18/25, 95% CI 50·6-87·9) and that of symptom screening alone was 36·0% (9/25, 18·0-57·5). Specificity of point-of-care C-reactive protein testing combined in parallel with symptom screening in people living with HIV was 47·0% (118/251, 95% CI 40·7-53·4) versus 72·1% (181/251, 66·1-77·6) with symptom screening alone. INTERPRETATION: Point-of-care C-reactive protein testing alone does not meet the 90% sensitivity stipulated by WHO's target product profile for desirable characteristics for screening tests for detecting tuberculosis. However, combined with symptom screening, it might improve identification of individuals with tuberculosis in communities with high prevalence, and might be particularly useful where other recommended tools, such as chest x-ray, might not be readily available. FUNDING: European and Developing Countries Clinical Trials Partnership.
Subject(s)
HIV Infections , Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Adult , Male , Humans , Female , Cross-Sectional Studies , C-Reactive Protein , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/epidemiology , Tuberculosis, Pulmonary/drug therapy , South Africa/epidemiology , Zambia/epidemiology , Point-of-Care Systems , Prospective Studies , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Sensitivity and Specificity , HIV Infections/diagnosis , HIV Infections/epidemiology , HIV Infections/drug therapyABSTRACT
BACKGROUND: The Xpert MTB/RIF Ultra (Xpert-Ultra) assay provides timely results with good sensitivity and acceptable specificity with stool specimens in children for bacteriological confirmation of tuberculosis (TB). This study aims to optimize the Simple One-Step (SOS) stool processing method for testing stool specimens using the Xpert-Ultra in children and adults in selected health facilities in Addis Ababa, Ethiopia. The study is designed to assess the robustness of the SOS stool method, to help fine-tune the practical aspects of performing the test and to provide insights in stool storage conditions and sampling strategies before the method can be implemented and scaled in routine settings in Ethiopia as well as globally. METHODS AND DESIGN: The project "painless optimized diagnosis of TB in Ethiopian children" (PODTEC) will be a cross sectional study where three key experiments will be carried out focusing on 1) sampling strategy to investigate if the Xpert-Ultra M. tuberculosis (MTB) -positivity rate depends on stool consistency, and if sensitivity can be increased by taking more than one stool specimen from the same participant, or doing multiple tests from the same stool specimen, 2) storage conditions to determine how long and at what temperature stool can be stored without losing sensitivity, and 3) optimization of sensitivity and robustness of the SOS stool processing method by varying stool processing steps, stool volume, and storage time and conditions of the stool-sample reagent mixture. Stool specimens will be collected from participants (children and adults) who are either sputum or naso-gastric aspiration (NGA) and/or stool Xpert-Ultra MTB positive depending on the experiment. Stool specimens from these participants, recruited from 22 sites for an ongoing related study, will be utilized for the PODTEC experiments. The sample size is estimated to be 50 participants. We will use EpiData for data entry and Stata for data analysis purposes. The main analyses will include computing the loss or gain in the Xpert-Ultra MTB positivity rate and rates of non-determinate Xpert-Ultra test results per experiment compared to the Xpert-Ultra MTB result of stool processed according to the published standard operating procedures for SOS stool processing. The differences in the MTB positivity rate by regarding testing more than one sample per child, and using different storage, and processing conditions, will be also compared to the baseline (on-site) Xpert-Ultra result.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Adult , Child , Cross-Sectional Studies , Ethiopia , Humans , Sensitivity and Specificity , Sputum , Tuberculosis/diagnosis , Tuberculosis, Pulmonary/diagnosisABSTRACT
BACKGROUND: Executive functions are pivotal for future academic and social functioning. Causal effects of physical activity on executive functions have been shown in adults. The primary objective of this study was to test the proof-of-concept (i.e., feasibility of implementation and acceptance) of a motor coordination intervention and a sedentary control condition in kindergartners and its preliminary effectiveness on subsequent executive function performance. METHODS: The study used a two-group post-test only design. All children aged between 4 and 7 years old were eligible. One hundred and three children (46% girls; age: M = 5.71 years, 95% CI = 5.50 to 5.92) recruited in a middle-sized town in Germany were randomly assigned to a 20-min motor coordination intervention (n = 51) or a sedentary control condition (n = 52), both of which were conducted in a one-on-one experimenter-child setting in the university or kindergarten. A second blinded-to-condition experimenter assessed the executive function outcomes directly following the conditions. Proof-of-concept criteria were the implementation of the intervention with a moderate-to-vigorous physical activity level assessed via heart rate sensors, and with motor coordination demands, analyzed via video recordings; children's acceptance via self-reported enjoyment of the conditions; and the post-assessments of executive functions with a behavioral and computerized task. RESULTS: The motor coordination intervention and the control condition were feasible in a one-on-one setting with kindergartners. The intervention revealed heart rate increases and challenging motor coordination tasks. Children in both conditions indicated they enjoy them. Performance in the two executive function tasks did not differ between children in the motor coordination intervention and the control condition. CONCLUSIONS: A one-on-one experimenter-child setting was feasible to deliver in kindergartners. Future intervention studies should consider pre-testing of executive functions and take into account children's characteristics as potential moderators, such as motor coordination skills.
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OBJECTIVES: The WHO currently recommends stool testing using GeneXpert MTB/Rif (Xpert) for the diagnosis of paediatric tuberculosis (TB). The simple one-step (SOS) stool method enables processing for Xpert testing at the primary healthcare (PHC) level. We modelled the impact and cost-effectiveness of implementing the SOS stool method at PHC for the diagnosis of paediatric TB in Ethiopia and Indonesia, compared with the standard of care. SETTING: All children (age <15 years) presenting with presumptive TB at primary healthcare or hospital level in Ethiopia and Indonesia. PRIMARY OUTCOME: Cost-effectiveness estimated as incremental costs compared with incremental disability-adjusted life-years (DALYs) saved. METHODS: Decision tree modelling was used to represent pathways of patient care and referral. We based model parameters on ongoing studies and surveillance, systematic literature review, and expert opinion. We estimated costs using data available publicly and obtained through in-country expert consultations. Health outcomes were based on modelled mortality and discounted life-years lost. RESULTS: The intervention increased the sensitivity of TB diagnosis by 19-25% in both countries leading to a 14-20% relative reduction in mortality. Under the intervention, fewer children seeking care at PHC were referred (or self-referred) to higher levels of care; the number of children initiating anti-TB treatment (ATT) increased by 18-25%; and more children (85%) initiated ATT at PHC level. Costs increased under the intervention compared with a base case using smear microscopy in the standard of care resulting in incremental cost-effectiveness ratios of US$132 and US$94 per DALY averted in Ethiopia and Indonesia, respectively. At a cost-effectiveness threshold of 0.5×gross domestic product per capita, the projected probability of the intervention being cost-effective in Ethiopia and Indonesia was 87% and 96%, respectively. The intervention remained cost-effective under sensitivity analyses. CONCLUSIONS: The addition of the SOS stool method to national algorithms for diagnosing TB in children is likely to be cost-effective in both Ethiopia and Indonesia.
Subject(s)
Sputum , Tuberculosis , Adolescent , Child , Cost-Benefit Analysis , Ethiopia , Humans , Indonesia , Tuberculosis/diagnosisABSTRACT
BACKGROUND: Xpert MTB/Rif, a molecular test to detect tuberculosis (TB), has been proven to have high sensitivity and specificity when compared with liquid culture in clinical settings. However, little is known about its performance in community TB screening. METHODS: In Vietnam, a national TB prevalence survey was conducted in 2017. Survey participants who screened positive by chest X-ray, cough symptoms and/or recent history of tuberculosis were requested to provide at least two sputum samples that were tested for Mycobacterium tuberculosis by Xpert MTB/Rif G4 (Xpert) and BACTEC MGIT960 culture (MGIT). RESULTS: There were 4,649 eligible participants provided both samples for testing. Among them, 236 (5.1%) participants tested positive for TB by Xpert, 244 (5.3%) tested positive by MGIT and 317 tested positive by at least one test; 163 (51.4%) had discordant test results. Of the positive Xpert, 162 (68.6%) showed a low or very low bacterial load. In multivariate logistic regression comparing discordant with Xpert-MGIT concordant positive results, discordant Xpert-positive results occurred more often among participants who had low sputum bacterial load, male sex, a history of TB treatment, or night sweats. The associated factors were male sex, abnormal chest X-ray and having night sweats when the logistic model was against those with both Xpert and MGIT negative. CONCLUSIONS: We found high rates of discordance in the performance of Xpert and MGIT for community-based TB case finding. In situations where the majority of TB cases are expected to have a low bacterial load, multiple diagnostic tests and/or multiple samples are required to reach sufficient sensitivity.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Lymph Node , Female , Humans , Male , Mycobacterium tuberculosis/genetics , Sensitivity and Specificity , Sputum/microbiology , Vietnam/epidemiologyABSTRACT
OBJECTIVES: Prevalence surveys remain the best way to assess the national tuberculosis (TB) burden in many countries. Challenges with using culture (the reference standard) for TB diagnosis in prevalence surveys have led to increasing use of molecular tests (Xpert assays), but discordance between these two tests has created problems for deciding which individuals have TB. We aimed to design an accurate diagnostic algorithm for TB prevalence surveys (TBPS) that limits the use of culture. DESIGN: TBPS in four communities, conducted during 2019. SETTING: Three Zambian communities and one South-African community included in the TBPS of the Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening study. PARTICIPANTS: Randomly sampled individuals aged ≥15 years. Among those who screened positive on chest X-ray or symptoms, two sputum samples were collected for field Xpert-Ultra testing and a third for laboratory liquid-culture testing. Clinicians reviewed screening and test results; in Zambia, participants with Mycobacterium tuberculosis-positive results were followed up 6-13 months later. Among 10 984 participants, 2092 screened positive, 1852 provided two samples for Xpert-Ultra testing, and 1009 had valid culture results. OUTCOMES: Culture and Xpert-Ultra test results. RESULTS: Among 946 culture-negative individuals, 917 were Xpert-negative, 12 Xpert-trace-positive and 17 Xpert-positive (grade very low, low, medium or high), with Xpert categorised as the highest grade of the two sample results. Among 63 culture-positive individuals, 8 were Xpert-negative, 9 Xpert-trace-positive and 46 Xpert-positive. Counting trace-positive results as positive, the sensitivity of Xpert-Ultra compared with culture was 87% (95% CI 76% to 94%) using two samples compared with 76% (95% CI 64% to 86%) using one. Specificity was 97% when trace-positive results were counted as positive and 98% when trace-positive results were counted as negative. Most Xpert-Ultra-positive/culture-negative discordance was among individuals whose Xpert-positive results were trace-positive or very low grade or they reported previous TB treatment. Among individuals with both Xpert-Ultra results grade low or above, the positive-predictive-value was 90% (27/30); 3/30 were plausibly false-negative culture results. CONCLUSION: Using Xpert-Ultra as the primary diagnostic test in TBPS, with culture only for confirmatory testing, would identify a high proportion of TB cases while massively reducing survey culture requirements. TRIAL REGISTRATION NUMBER: NCT03739736.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Humans , Mycobacterium tuberculosis/genetics , Prevalence , Sensitivity and Specificity , South Africa/epidemiology , Sputum/microbiology , Tuberculosis/diagnosis , Tuberculosis/epidemiology , Tuberculosis, Pulmonary/diagnosis , Zambia/epidemiologyABSTRACT
Young children cannot easily produce sputum for diagnosis of pulmonary tuberculosis (TB). Alternatively, Mycobacterium tuberculosis complex bacilli can be detected in stool by using the Xpert MTB/RIF (Ultra) assay (Xpert). Published stool processing methods contain somewhat complex procedures and require additional supplies. The aim of this study was to develop a simple one-step (SOS) stool processing method based on gravity sedimentation only, similar to Xpert testing of sputum samples, for the detection of M. tuberculosis in stool samples. We first assessed whether the SOS stool method could provide valid Xpert results without the need for bead-beating, dilution, and filtration steps. We concluded that this was the case, and we then validated the SOS stool method by testing spiked stool samples. By using the SOS stool method, 27 of the 29 spiked samples gave valid Xpert results, and M. tuberculosis was recovered from all 27 samples. The proof of principle of the SOS stool method was demonstrated in routine settings in Addis Ababa, Ethiopia. Nine of 123 children with presumptive TB had M. tuberculosis-positive results for nasogastric aspiration (NGA) samples, and 7 (77.8%) of those children also had M. tuberculosis-positive Xpert results for stool samples. Additionally, M. tuberculosis was detected in the stool samples but not the NGA samples from 2 children. The SOS stool processing method makes use of the standard Xpert assay kit, without the need for additional supplies or equipment. The method can potentially be rolled out to any Xpert site, bringing a bacteriologically confirmed diagnosis of TB in children closer to the point of care.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis , Child, Preschool , Ethiopia , Humans , Mycobacterium tuberculosis/genetics , Point-of-Care Systems , Sensitivity and Specificity , Sputum , Tuberculosis/diagnosisABSTRACT
Physical activity declines from childhood to adolescence. Affective factors may partially account for this decline. The present study investigated whether within-person changes in children's enjoyment of physical activity are associated with the age-related decline in physical activity. Children (N = 169, 54% female, 56% Hispanic; 8-12 years old at enrollment) took part in a longitudinal study with six assessment waves across 3 years. At each wave, enjoyment of physical activity was reported, and moderate to vigorous physical activity (MVPA) was measured with an accelerometer across seven consecutive days. MVPA and enjoyment of physical activity both declined across waves. Multilevel analyses revealed that within-person changes in enjoyment moderated the effects of age on within-person changes in MVPA. Enjoyment appeared to be a dynamic factor that buffered against the age-related decline in physical activity in youth. These findings call for health promotion interventions that encourage enjoyable physical activities.
Subject(s)
Exercise , Pleasure , Adolescent , Child , Emotions , Female , Humans , Longitudinal Studies , MaleABSTRACT
Vietnam, a high tuberculosis (TB) burden country, conducted national TB prevalence surveys in 2007 and 2017. In both surveys participants were screened by using a questionnaire and chest radiograph; sputum samples were then collected to test for Mycobacterium tuberculosis by smear microscopy and Löwenstein-Jensen culture. Culture-positive, smear-positive, and smear-negative TB cases were defined by laboratory results, and the prevalence of tuberculosis was compared between the 2 surveys. The results showed prevalence of culture-positive TB decreased by 37% (95% CI 11.5%-55.4%), from 199 (95% CI 160-248) cases/100,000 adults in 2007 to 125 (95% CI 98-159) cases/100,000 adults in 2017. Prevalence of smear-positive TB dropped by 53% (95% CI 27.0%-69.7%), from 99 (95% CI 78-125) cases/100,000 adults to 46 (95% CI 32-68) cases/100,000 adults; smear-negative TB showed no substantial decrease. Replacing microscopy with molecular methods for primary diagnostics might enhance diagnosis of pulmonary TB cases and further lower TB burden.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis, Pulmonary , Tuberculosis , Adult , Diagnostic Tests, Routine , Humans , Sensitivity and Specificity , Sputum , VietnamABSTRACT
[This corrects the article DOI: 10.1371/journal.pone.0232142.].
ABSTRACT
INTRODUCTION: Tuberculosis (TB) remains a significant cause of morbidity and mortality in Vietnam. The current TB burden is unknown as not all individuals with TB are diagnosed, recorded and notified. The second national TB prevalence survey was conducted in 2017-2018 to assess the current burden of TB disease in the country. METHOD: Eighty-two clusters were selected using a multistage cluster sampling design. Adult (≥15 years of age) residents having lived for 2 weeks or more in the households of the selected clusters were invited to participate in the survey. The survey participants were screened for TB by a questionnaire and digital chest X-ray after providing written informed consent. Individuals with a positive symptom screen and/or chest X-ray suggestive of TB were asked to provide sputum samples to test for Mycobacterium tuberculosis by Ziehl-Neelsen direct light microscopy, Xpert MTB/RIF G4, BACTEC MGIT960 liquid culture and Löwenstein-Jensen solid culture. Bacteriologically confirmed TB cases were defined by an expert panel following a standard decision tree. RESULT: Of 87,207 eligible residents, 61,763 (70.8%) participated, and 4,738 (7.7%) screened positive for TB. Among these, 221 participants were defined as bacteriologically confirmed TB cases. The estimated prevalence of bacteriologically confirmed adult pulmonary TB was 322 (95% CI: 260-399) per 100,000, and the male-to-female ratio was 4.0 (2.8-5.8, p<0.001). In-depth interviews with the participants with TB disease showed that only 57.9% (95% CI: 51.3-64.3%) reported cough for 2 weeks or more and 32.1% (26.3-38.6%) did not report any symptom consistent with TB, while their chest X-ray results showed that 97.7% (95% CI: 94.6-99.1) had abnormal chest X-ray images suggesting TB. CONCLUSION: With highly sensitive diagnostics applied, this survey showed that the TB burden in Vietnam remains high. Half of the TB cases were not picked up by general symptom-based screening and were identified by chest X-ray only. Our results indicate that improving TB diagnostic capacity and access to care, along with reducing TB stigma, need to be top priorities for TB control and elimination in Vietnam.