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Xpert MTB/RIF Ultra (Ultra)-detected rifampicin-resistant tuberculosis (TB) is often programmatically confirmed using MTBDR plus . There are limited data on discordant results, including when re-tested using newer methods, like FluoroType MTBDR (FT-MTBDR) and targeted deep sequencing. MTBDR plus rifampicin-susceptible isolates from people with Ultra rifampicin-resistant sputum were identified from a South African programmatic laboratory. FT-MTBDR and single molecule-overlapping reads (SMOR; rpoB , inhA , katG ) on isolate DNA were done (SMOR was used as a reference standard). Between 1 April 2021 and 30 September 2022, 8% (109/1347) of Ultra rifampicin-resistant specimens were MTBDR plus -susceptible. Of 89% (97/109) isolates with a sequenceable rpoB , SMOR resolved most in favor of Ultra (79% [77/97]). Sputum with lower mycobacterial load was associated with Ultra false-positive resistance (46% [11/24] of "very low" Ultra had false resistance vs 12% [9/73; P = 0.0004] of ≥"low"), as were Ultra heteroresistance calls (all wild-type probes, ≥1 mutant probe) (62% [23/37 vs 25% 15/60] for Ultra without heteroresistance calls; P = 0.0003). Of the 91% (88/97) of isolates successfully tested by FT-MTBDR, 55% (48/88) were FT-MTBDR rifampicin-resistant and 45% (40/88) susceptible, translating to 69% (47/68) sensitivity and 95% (19/20) specificity. In the 91% (99/109) of isolates with inhA and katG sequenced, 62% (61/99) were SMOR isoniazid-susceptible. When Ultra and MTBDR plus rifampicin results are discordant, Ultra is more likely to be correct, and FT-MTBDR agrees more with Ultra than MTBDR plus ; however, lower load and the Ultra heteroresistance probe pattern were risk factors for Ultra false rifampicin-resistant results. Most people with Ultra-MTBDR plus discordant resistance results were isoniazid-susceptible. These data have implications for drug-resistant TB diagnosis., Competing Interests: The authors declare no conflict of interest.

Purpose: To determine the association between the severity of trachomatous conjunctival scarring (TS) of the upper eyelid conjunctiva and trachomatous trichiasis (TT) severity in TT surgical patients., Methods: A cross-sectional study was conducted amongst adults with TT who were referred to surgical camps in Bahi District, Tanzania, for TT surgery. Participants underwent ocular examination. The presence and severity of TS was evaluated in photographs of the everted upper eyelid. TT severity was assessed at the time of the ocular exam based on the number of lashes touching the globe and/or evidence and extent of epilation. Ordinal logistic models were used to examine the association between the severity of TS and TT severity., Results: A total of 627 eyes of 388 participants were included. Mean age was 65 years (ranging from 21-98), 81% were females, and 62% had bilateral TT. 93% of eyes with any TT had at least moderate TS; 62% of eyes had severe TS. An increase in TS severity was associated with an increase in the severity of TT. Using as a reference eyes with none to mild TS, in eyes with moderate TS the odds of increased severity of TT was 1.30 (95% CI 0.67-2.51), in eyes with severe TS the odds was 4.20 (95% CI 2.23-7.92)., Conclusion: In cases of trachomatous trichiasis presenting for surgery, the severity of TT was significantly associated with the severity of TS with almost all cases of TT having moderate or severe scarring.

Purpose: As training of trachoma graders using live participants grows increasingly difficult and expensive, alternative ways are needed possibly through replacement of field grading with photography. However, minimum specifications for a camera system capable of capturing high quality images have not been defined. This study compared images captured using four smartphones with those from a Nikon SLR camera for image quality and assessment of trachomatous inflammation - follicular (TF)., Methods: The smartphones - Samsung Galaxy S8 (S8), Techno Camon 17 pro (TC), Infinix Note 10 pro (IN), Huawei p30 pro (HP) - were chosen for their availability and likelihood of good performance based on specifications without external attachments. All smartphones were used in random order for each participant., Results: 129 children in Kongwa, Tanzania were enrolled (32.8% TF prevalence). The SLR camera had the least percent of ungradable images (3.1%), followed by the S8 (14%), HP (23.4%), IN (65.9%), and TC (71.2%). The S8 and the HP were significantly more likely to take ungradable images if they were used toward the end of the camera rotation. Agreement between the SLR and field grade was kappa = 0.73. Agreement between the field grade and gradable images from the S8 (0.68) and HP (0.8) was measured., Conclusions: Published specifications did not predict the success of using different smartphones for everted eyelid photographs; proprietary post-processing software likely influenced gradeability. Smartphones, though we cannot recommend those tested in this study, may be viable for capturing images for trachoma provided the quality of images from the field are adequate.

Importance: Rifampin-resistant tuberculosis treatment regimens require electrocardiographic (ECG) monitoring due to the use of multiple QTc-prolonging agents. Formal 12-lead ECG devices represent a significant burden in resource-constrained clinics worldwide and a potential barrier to treatment scale-up in some settings., Objective: To evaluate the diagnostic accuracy of a handheld 6-lead ECG device within resource-constrained clinics., Design, Setting, and Participants: This diagnostic study was performed within a multicenter, pragmatic (broad eligibility criteria with no exclusions for randomized participants), phase 3 rifampin-resistant tuberculosis treatment trial (BEAT Tuberculosis [Building Evidence for Advancing New Treatment for Tuberculosis]) in South Africa. A total of 192 consecutive trial participants were assessed, and 191 were recruited for this substudy between January 21, 2021, and March 27, 2023. A low proportion (3 of 432 [0.7%]) of all screened trial participants were excluded due to a QTc interval greater than 450 milliseconds. Triplicate reference standard 12-lead ECG results were human calibrated with readers blinded to 6-lead ECG results., Main Outcomes and Measures: Diagnostic accuracy, repeatability, and feasibility of a 6-lead ECG device., Results: A total of 191 participants (median age, 36 years [IQR, 28-45 years]; 81 female participants [42.4%]; 91 participants [47.6%] living with HIV) with a median of 4 clinic visits (IQR, 3-4 visits) contributed 2070 and 2015 12-lead and 6-lead ECG assessments, respectively. Across 170 participants attending 489 total clinic visits where valid triplicate QTc measurements were available for both devices, the mean 12-lead QTc measurement was 418 milliseconds (range, 321-519 milliseconds), and the mean 6-lead QTc measurement was 422 milliseconds (range, 288-574 milliseconds; proportion of variation explained, R2 = 0.4; P < .001). At a QTc interval threshold of 500 milliseconds, the 6-lead ECG device had a negative predictive value of 99.8% (95% CI, 98.8%-99.9%) and a positive predictive value of 16.7% (95% CI, 0.4%-64.1%). The normal expected range of within-individual variability of the 6-lead ECG device was high (±50.2 milliseconds [coefficient of variation, 6.0%]) relative to the 12-lead ECG device (±22.0 milliseconds [coefficient of variation, 2.7%]). The mean (SD) increase in the 12-lead QTc measurement during treatment was 10.1 (25.8) milliseconds, with 0.8% of clinic visits (4 of 489) having a QTc interval of 500 milliseconds or more., Conclusions and Relevance: This study suggests that simplified, handheld 6-lead ECG devices are effective triage tests that could reduce the need to perform 12-lead ECG monitoring in resource-constrained settings.

Background: Trachoma is a chronic conjunctivitis caused by the bacterium Chlamydia trachomatis. Repeated infections lead to trachomatous conjunctival scarring which can progress to potentially blinding trachomatous trichiasis (TT). In trachoma hyperendemic conditions, women compared to men have an increased risk of scarring and TT, which can progress to blinding corneal opacification. This study determined if there were gender differences in scarring prevalence and severity when trachoma prevalence approaches elimination, in a formerly trachoma hyperendemic region., Methodology/principal Findings: A cross-sectional prevalence study was conducted amongst adults age 15 years and older in Kongwa district, Tanzania in 2019. 3168 persons over age 15 years agreed to be examined and had at least one eye with a gradable image. Ocular photographs were graded for scarring according to a published four-step severity scale. Overall, about half of all study participants had scarring. However, more females (52.3%) had any scarring compared to males (47.2%), OR = 1.22 (95% CI = 1.05-1.43). For every year increase in age, there was a 6.5% increase in the odds of having more severe scarring (95% CI: 5.8%, 7.2%). Women were more likely than men to have severe scarring, OR 2.36 (95% CI: 1.84-3.02). Residence in a community with TF≥10% was associated with a 1.6-fold increased odds of any scarring., Conclusions/significance: Overall scarring prevalence and more severe scarring prevalence was higher in females compared to males, even adjusting for age and community TF prevalence. The data suggest that processes occur that lead to women preferentially progressing towards more severe scarring compared to men., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wolle et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: Improving detection of pediatric tuberculosis (TB) is critical to reducing morbidity and mortality among children., Objective: We conducted a systematic review to estimate the number of children needed to screen (NNS) to detect a single case of active TB using different active case finding (ACF) screening approaches and across different settings., Data Sources: We searched 4 databases (PubMed, Embase, Scopus, and the Cochrane Library) for articles published from November 2010 to February 2020., Study Selection: We included studies of TB ACF in children using symptom-based screening, clinical indicators, chest x-ray, and Xpert., Data Extraction: We indirectly estimated the weighted mean NNS for a given modality, location, and population using the inverse of the weighted prevalence. We assessed risk of bias using a modified AXIS tool., Results: We screened 27 221 titles and abstracts, of which we included 31 studies of ACF in children < 15 years old. Symptom-based screening was the most common screening modality (weighted mean NNS: 257 [range, 5-undefined], 19 studies). The weighted mean NNS was lower in both inpatient (216 [18-241]) and outpatient (67 [5-undefined]) settings (107 [5-undefined]) compared with community (1117 [28-5146]) and school settings (464 [118-665]). Risk of bias was low., Limitations: Heterogeneity in the screening modalities and populations make it difficult to draw conclusions., Conclusions: We identified a potential opportunity to increase TB detection by screening children presenting in health care settings. Pediatric TB case finding interventions should incorporate evidence-based interventions and local contextual information in an effort to detect as many children with TB as possible., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Active case finding (ACF) for tuberculosis (TB) is the cornerstone case-finding strategy in India's national TB policy. However, ACF strategies are highly diverse and pose implementation challenges in routine programming. We reviewed the literature to characterise ACF in India; assess the yield of ACF for different risk groups, screening locations, and screening criteria; and estimate losses to follow-up (LTFU) in screening and diagnosis., Methods: We searched PubMed, EMBASE, Scopus, and the Cochrane library to identify studies with ACF for TB in India from November 2010 to December 2020. We calculated 1) weighted mean number needed to screen (NNS) stratified by risk group, screening location, and screening strategy; and 2) the proportion of screening and pre-diagnostic LTFU. We assessed risk of bias using the AXIS tool for cross-sectional studies., Findings: Of 27,416 abstracts screened, we included 45 studies conducted in India. Most studies were from southern and western India and aimed to diagnose pulmonary TB at the primary health level in the public sector after screening. There was considerable heterogeneity in risk groups screened and ACF methodology across studies. Of the 17 risk groups identified, the lowest weighted mean NNS was seen in people with HIV (21, range 3-89, n =5), tribal populations (50, range 40-286, n =3), household contacts of people with TB (50, range 3-undefined, n =12), people with diabetes (65, range 21-undefined, n =3), and rural populations (131, range 23-737, n =5). ACF at facility-based screening (60, range 3-undefined, n =19) had lower weighted mean NNS than at other screening locations. Using the WHO symptom screen (135, 3-undefined, n =20) had lower weighted mean NNS than using criteria of abnormal chest x-ray or any symptom. Median screening and pre-diagnosis loss-to-follow-up was 6% (IQR 4.1%, 11.3%, range 0-32.5%, n =12) and 9.5% (IQR 2.4%, 34.4%, range 0-86.9%, n =27), respectively., Interpretation: For ACF to be impactful in India, its design must be based on contextual understanding. The narrow evidence base available currently is insufficient for effectively targeting ACF programming in a large and diverse country. Achieving case-finding targets in India requires evidence-based ACF implementation., Funding: WHO Global TB Programme., Competing Interests: LHC, FN, and JEG declare funding from the WHO TB Programme for the systematic review of active case finding for TB. TG and JEG are authors of studies included in this systematic review. The views and information presented are our own. The WHO, NIH, and Fulbright-Nehru Master's Fellowship had no role in the conduct of the study or writing the review. All other authors declare no competing interests., (© 2022 The Author(s).)

As trachoma prevalence declines worldwide, performing field surveys with trained trachoma graders to validate its elimination becomes challenging. Graded conjunctival images could be used to train graders, validate field grades, and replace field grading. We review the use of photography to capture conjunctival images for the detection of trachomatous inflammation-follicular (TF) and -intense (TI), Trachomatous trichiasis (TT), and eyelid contour abnormalities. Literature searches were conducted between October 29, 2020 and February 15, 2021. We abstracted kappa scores for agreement between field and image graders, between field graders, and between image graders. The median kappa was calculated for studies discussing grading for TF and TI. Twenty-one studies were included - 19 described the use of imaging tools for grading TF and TI; 1 discussed TT; and 1 discussed eyelid contour abnormalities. For agreement between field and image graders, median kappa for TF was 0.71 (range: 0.57-0.92) and TI was 0.67 (0.37-0.74); between image graders, median kappa for TF was 0.65 (0.37-0.78) and TI was 0.76 (0.39-0.83); and between field graders, median kappa for TF was 0.86 (0.73-1) and TI was 0.82 (0.73-0.91). There is potential for the use of photography for trachoma prevalence surveys. Further research is warranted, particularly for TT and using newer smartphones., Competing Interests: Conflict of interest The authors declare that there are no conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Graded images can be used for trachoma prevalence surveys, but there is concern for mismatch between image and field grades of the upper tarsal conjunctiva. We aimed to determine if poor photograph quality and/or inflammation may contribute to differential grading of trachomatous inflammation-follicular (TF) between field and photograph graders., Methods: We developed a simplified and expanded image quality grading tool. Agreement was assessed using kappa statistic. We included 5417 eyes with both field and image grades for TF. Eyes where the field and adjudicated photograph TF grades did not match were identified (mismatched) and assigned an image quality (IQ) score and a potential mismatch reason. We also assigned IQ scores to a stratified random sample of 60 eyes with matching field and photograph TF grades (matched)., Results: There were 5240 eyes that had matching grades, whereas 177 eyes (3.3%) were mismatched. Overall quality was high, even in mismatched eyes. There was no difference in overall or specific IQ metrics between eyes with matching grades and eyes with mismatched grades (P = 0.59). Mismatched eyes had worse inflammation compared to matched eyes (P = 0.048). The primary reason for calling TF in the field but not in the photographs appeared to be the number of follicles observed., Conclusions: Image quality did not explain mismatch between field grades and image grades from this prevalence survey. Inflammation made mismatch more likely., Translational Relevance: Our quality grading scheme rapidly identifies image quality issues for training. Standardizing TF grading in the presence of inflammation will improve field and photograph grading.

Background: Clinical trials for retinitis pigmentosa (RP) likely require long follow-ups because of the slow progression of RP. Understanding patients' attitudes toward participation in a long trial and their acceptability of strategies aimed at promoting retention/compliance is important for assessing feasibility and resource needs and optimizing trial design., Methods: A crowdsourcing survey to adult RP patients was administered on social media in 2020 July-November. Patient enthusiasm level of study participation, acceptability of attending clinic visits every 4-5 months for 45-months, tele-visits with doctors, and of receiving text messages for medication reminders and for reporting missed dosages were surveyed., Results: Among the 1473 respondents, over 95% use email or a mobile phone and receive text messages; 1157 (79%) respondents were very/somewhat enthusiastic about participation, among them, 80.6% were "very willing" to attend clinic visits every 4-5 months for 45 months; 90.3% were "very willing" to have tele-visits; 64.7% and 77.1% were willing to receive text reminders to take medication and messages surveying missed doses, respectively. The youngest age group (18-30) (22.1%) and oldest age group (70+) (26.1%) compared to the 41-50 years age group (14%) and women (23.5%) compared to men (14.2%) were statistically significantly more likely not to report high willingness to participate in clinical visits for 45 months., Conclusions: A trial requiring 4-years of commitment is feasible although retention can be challenging. Strategies including supplementing in-clinic visits with tele-visits and frequent communications may facilitate retention. This study also demonstrates a methodology useful for planning clinical trials for chronic diseases.

Community-based active case-finding (ACF) may have important impacts on routine TB case-detection and subsequent patient-initiated diagnosis pathways, contributing "indirectly" to infectious diseases prevention and care. We investigated the impact of ACF beyond directly diagnosed patients for TB, using routine case-notification rate (CNR) ratios as a measure of indirect effect. We systematically searched for publications 01-Jan-1980 to 13-Apr-2020 reporting on community-based ACF interventions compared to a comparison group, together with review of linked manuscripts reporting knowledge, attitudes, and practices (KAP) outcomes or qualitative data on TB testing behaviour. We calculated CNR ratios of routine case-notifications (i.e. excluding cases identified directly through ACF) and compared proxy behavioural outcomes for both ACF and comparator communities. Full text manuscripts from 988 of 23,883 abstracts were screened for inclusion; 36 were eligible. Of these, 12 reported routine notification rates separately from ACF intervention-attributed rates, and one reported any proxy behavioural outcomes. Two further studies were identified from screening 1121 abstracts for linked KAP/qualitative manuscripts. 8/12 case-notification studies were considered at critical or serious risk of bias. 8/11 non-randomised studies reported bacteriologically-confirmed CNR ratios between 0.47 (95% CI:0.41-0.53) and 0.96 (95% CI:0.94-0.97), with 7/11 reporting all-form CNR ratios between 0.96 (95% CI:0.88-1.05) and 1.09 (95% CI:1.02-1.16). One high-quality randomised-controlled trial reported a ratio of 1.14 (95% CI 0.91-1.43). KAP/qualitative manuscripts provided insufficient evidence to establish the impact of ACF on subsequent TB testing behaviour. ACF interventions with routine CNR ratios >1 suggest an indirect effect on wider TB case-detection, potentially due to impact on subsequent TB testing behaviour through follow-up after a negative ACF test or increased TB knowledge. However, data on this type of impact are rarely collected. Evaluation of routine case-notification, testing and proxy behavioural outcomes in intervention and comparator communities should be included as standard methodology in future ACF campaign study designs., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JEG, HA, and ELC are authors of trials included in this systematic review. HA and ELC are members of the WHO TB Screening Guideline Development Group, which CM co-ordinates. JEG, HA, ELC, and PM have received research grants to their institutions for projects evaluating community-based active case-finding. All other authors declare no competing interests., (Copyright: © 2021 Feasey et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Trachoma, a chronic conjunctivitis caused by Chlamydia trachomatis, is the leading infectious cause of blindness worldwide. Trachoma has been targeted for elimination as a public health problem which includes reducing trachomatous inflammation-follicular prevalence in children and reducing trachomatous trichiasis prevalence in adults. The rate of development of trachomatous trichiasis, the potentially blinding late-stage trachoma sequelae, depends on the rate of trachomatous scarring development and progression. Few studies to date have evaluated the progression of trachomatous scarring in communities that have recently transitioned to a low trachomatous inflammation-follicular prevalence., Methodology/principal Findings: Women aged 15 and older were randomly selected from households in 48 communities within Kongwa district, Tanzania and followed over 3.5 years for this longitudinal study. Trachomatous inflammation-follicular prevalence was 5% at baseline and at follow-up in children aged 1-9 in Kongwa, Tanzania. 1018 women aged 15 and older had trachomatous scarring at baseline and were at risk for trachomatous scarring progression; 691 (68%) completed follow-up assessments. Photographs of the upper tarsal conjunctiva were obtained at baseline and follow-up and graded for trachomatous scarring using a previously published four-step severity scale. The overall cumulative 3.5-year progression rate of scarring was 35.3% (95% CI 31.6-39.1). The odds of TS progression increased with an increase in age in women younger than 50, (OR 1.03, 95% CI 1.01-1.05, p = 0.005) as well as an increase in the household poverty index (OR 1.29, 95% CI 1.13-1.48, p = 0.0002)., Conclusions/significance: The 3.5-year progression of scarring among women in Kongwa, a formerly hyperendemic now turned hypoendemic district in central Tanzania, was high despite a low active trachoma prevalence. This suggests that the drivers of scarring progression are likely not related to on-going trachoma transmission in this district., Competing Interests: The authors have declared that no competing interests exist.

Background: As the prevalence of trachoma declines worldwide, it is becoming increasingly expensive and challenging to standardize graders in the field for surveys to document elimination. Photography of the tarsal conjunctiva and remote interpretation may help alleviate these challenges. The purpose of this study was to develop, and field test an Image Capture and Processing System (ICAPS) to acquire hands-free images of the tarsal conjunctiva for upload to a virtual reading center for remote grading., Methodology/principal Findings: This observational study was conducted during a district-level prevalence survey for trachomatous inflammation-follicular (TF) in Chamwino, Tanzania. The ICAPS was developed using a Samsung Galaxy S8 smartphone, a Samsung Gear VR headset, a foot pedal trigger and customized software allowing for hands-free photography. After a one-day training course, three trachoma graders used the ICAPS to collect images from 1305 children ages 1-9 years, which were expert-graded remotely for comparison with field grades. In our experience, the ICAPS was successful at scanning and assigning barcodes to images, focusing on the everted eyelid with adequate examiner hand visualization, and capturing images with sufficient detail to grade TF. The percentage of children with TF by photos and by field grade was 5%. Agreement between grading of the images compared to the field grades at the child level was kappa = 0.53 (95%CI = 0.40-0.66). There were ungradable images for at least one eye in 199 children (9.1%), with more occurring in children ages 1-3 (18.5%) than older children ages 4-9 (4.2%) (χ2 = 145.3, p<0.001)., Conclusions/significance: The prototype ICAPS device was robust, able to image 1305 children in a district level survey and transmit images from rural Tanzania to an online grading platform. More work is needed to improve the percentage of ungradable images and to better understand the causes of disagreement between field and photo grading., Competing Interests: The authors have declared that no competing interests exist.

Background: Having a clean face is protective against trachoma. In the past, long distances to water were associated with unclean faces and increased trachoma. Other environmental factors have not been extensively explored. We need improved clarity on the environmental factors associated with facial cleanliness and trachoma prevalence, especially when the disease burden is low., Methodology/principle Findings: A cross-sectional survey focusing on household environments was conducted in all 92 villages in Kongwa, Tanzania, in a random selection of 1798 households. Children aged 0-5 years in these households were examined for facial cleanliness. In each of the 50 randomly-selected villages, 50 children aged 1-9 years were randomly selected and examined for trachoma. In a multivariate model adjusting for child age, we found that children were more likely to have clean faces if the house had a clean yard (OR 1.62, 95% CI 1.37-1.91), an improved latrine (OR 1.11, 95% CI 1.01-1.22), and greater water storage capacity (OR 1.02, 95% CI 1.00-1.04), and if there were clothes washed and drying around the house (OR 1.30, 95% CI 1.09-1.54). However, measures of crowding, wealth, time spent on obtaining water, or the availability of piped water was not associated with clean faces. Using a cleanliness index (clean yard, improved latrine, washing clothes, ≥1 child in the household having a clean face), the community prevalence of trachoma decreased with an increase in the average value of the index (OR 2.28, 95% CI 1.17-4.80)., Conclusions/significance: Access to water is no longer a significant limiting factor in children's facial cleanliness in Kongwa. Instead, water storage capacity and the way that water is utilized are more important in facial cleanliness. A household cleanliness index with a holistic measure of household environment is associated with reduced community prevalence of trachoma., Competing Interests: The authors have declared that no competing interests exist.

Background: Community-based active case-finding interventions might identify and treat more people with tuberculosis disease than standard case detection. We aimed to assess whether active case-finding interventions can affect tuberculosis epidemiology in the wider community., Methods: We did a systematic review by searching PubMed, Embase, Scopus, and Cochrane Library for studies that compared tuberculosis case notification rates, tuberculosis disease prevalence, or tuberculosis infection prevalence or incidence in children, between populations exposed and unexposed to active case-finding interventions. We included studies published in English between Jan 1, 1980, and April 13, 2020. Studies of active case-finding in the general population, in populations perceived to be at high risk for tuberculosis, and in closed settings were included, whereas studies of tuberculosis screening at health-care facilities, among household contacts, or among children only, and studies that screened fewer than 1000 people were excluded. To estimate effectiveness, we extracted or calculated case notification rates, prevalence of tuberculosis disease, and incidence or prevalence of tuberculosis infection in children, and compared ratios of these outcomes between groups that were exposed or not exposed to active case-finding interventions., Results: 27 883 abstracts were screened and 988 articles underwent full text review. 28 studies contributed data for analysis of tuberculosis case notifications, nine for prevalence of tuberculosis disease, and two for incidence or prevalence of tuberculosis infection in children. In one cluster-randomised trial in South Africa and Zambia, an active case-finding intervention based on community mobilisation and sputum drop-off did not affect tuberculosis prevalence, whereas, in a cluster-randomised trial in Vietnam, an active case-finding intervention based on sputum tuberculosis tests for everyone reduced tuberculosis prevalence in the community. We found inconsistent, low-quality evidence that active case-finding might increase the number of cases of tuberculosis notified in populations with structural risk factors for tuberculosis., Interpretation: Community-based active case-finding for tuberculosis might be effective in changing tuberculosis epidemiology and thereby improving population health if delivered with high coverage and intensity. If possible, active case-finding projects should incorporate a well designed, robust evaluation to contribute to the evidence base and help elucidate which delivery methods and diagnostic strategies are most effective., Funding: WHO Global TB Programme., Competing Interests: Declaration of interests JEG, HA, and ELC are authors of trials included in this systematic review. HA and ELC are members of the WHO TB Screening Guideline Development Group. JEG, HA, ELC, and PM have received research grants to their institutions for projects evaluating community-based active case-finding. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: Knowledge of a patient's emotional health status and using patient-centred communication may be key to providing early intervention and referral to appropriate treatment/support services for ophthalmology patients. This study aims to determine if and how ophthalmologists use anxiety and depression scores to determine clinical care of patients with chronic eye disease., Methods and Analysis: This cross-sectional study included 10 ophthalmologists and a convenience sample of 100 of their patients (>18 years). The Patient Health Questionnaire (PHQ-9) for depression and the Generalised Anxiety Disorder (GAD-7) tool were administered to patients. Scores from these instruments were provided to ophthalmologists just prior to the clinic visit. After the visit, ophthalmologists were given a questionnaire to assess self-reported change in clinical practice and whether knowledge of scores impacted their communication style, treatment plan and follow-up protocol., Results: Of these patients (mean age=63), 27% reported mild-moderate anxiety or depression as their worst score, while 2% reported suicidal thoughts; 20% reported neither anxiety nor depression. Ophthalmologists' response to patients with mild or worse anxiety or depression was to change clinical approach (28%) and communication style (31%), both metrics increasing with severity of symptoms (Fisher's exact p<0.05). None reported changing their choice of treatment or modifying follow-up protocols; referral to social work/psychiatry services was 60%, 3.7% and 0% for patients with moderately severe or worse, mild-to-moderate, or minimal scores, respectively., Conclusion: Providing ophthalmologists with knowledge of the emotional health of their patients may change the clinical approach and referral pattern., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To eliminate trachoma as a public health problem, countries must achieve a district-level prevalence of trachomatous inflammation-follicular (TF) <5% in children ages 1-9 years. Re-emergence of TF could trigger additional rounds of mass drug/antibiotic administration (MDA), so accurate tools for use in surveys assessing trachoma prevalence are essential., Methodology & Principal Findings: We surveyed 2401 children ages 1-9 years from 50 villages in Kongwa, Tanzania, 2 years post-MDA and 1.5 years after an impact survey found TF <5% in the same villages. Our survey included multiple tools: clinical determination of TF, Cepheid testing for Chlamydia trachomatis infection, and testing for anti-pgp3 antibodies via multiplex bead array. Photographs of the upper tarsal conjunctiva were taken in a subset of children to corroborate the field grades. Overall TF prevalence in 1-9 year olds was 7.1% (95% CI: 5.6%-8.9%), which decreased with age (p = <0.0001). TF prevalence by village was heterogeneous, with 19 villages having TF <5% and 16 villages having TF >10%. There was a strong correlation between field and photo grading of TF (kappa = 0.69; 95% CI: 0.60-0.78) and between TF and infection, with 21.5% of TF-positive children also testing positive for infection, as compared to only 1.6% of TF-negative children (p = 0.0010). Overall seroprevalence was 18.2% (95% CI: 14.8%-22.1%), which increased with age (p = <0.0001). Notably, 1-2 year olds, who were born after the cessation of MDA and theoretically should not have had exposure to C. trachomatis in the absence of transmission, had an average seroprevalence of 6.7%., Conclusions & Significance: Field TF prevalence, supported by photographic review and infection data, suggested re-emergence of trachoma in Kongwa. Moreover, seropositivity in the children born after cessation of MDA indicated exposure to C. trachomatis despite a previous survey finding of TF <5%. Examining seropositivity in specific age groups expected to have limited exposure to C. trachomatis can be used to detect re-emergence., Competing Interests: The authors have declared that no competing interests exist.

Background: Trachoma is the leading infectious cause of blindness. Repeated or persistent ocular infection with Chlamydia trachomatis in childhood leads to conjunctival scarring, usually in adulthood but often earlier in areas with greater disease burden. There are limited longitudinal data examining change in scarring in children, especially where trachoma rates are low., Methodology/principal Findings: A cohort of children, ages 1-9 years, were randomly selected at baseline from 38 communities in Kongwa, Tanzania and followed for 2 years. Rates of trachomatous inflammation-follicular (TF) were <5% over the survey period. At baseline, 1,496 children were recruited and 1,266 (85%) were followed-up. Photographs were obtained at baseline and follow-up and graded for the presence and severity of scarring using a four-point scale ranging between S1-S4. In children without scarring at baseline, 1.6% (20/1,246) were found to have incident scarring, and incident scarring was more common among girls compared to boys. Among children with scarring at baseline, 21% (4/19) demonstrated progression., Conclusions/significance: In this formerly hyper-endemic district, the incidence of new scarring in children ages 1-9 years is low, although 21% of those who had scarring at baseline progressed in severity over the 2-year follow-up period. These data provide support for the thesis that while incident scarring more closely reflects ongoing exposure, progression may involve factors independent of ongoing transmission of trachoma., Competing Interests: The authors have declared that no competing interests exist.

Background: The dose of intravenous tissue plasminogen activator (tPA) administered in acute ischemic stroke patients is calculated using the patient's weight (0.9 mg/kg). Patients are rarely weighed before treatment in actual practice, although overestimating patient weights leads to higher doses of tPA, which may adversely influence outcome., Methods: We investigated the weight used to calculate the dose of tPA compared to the actual measured weight in consecutive acute ischemic stroke patients treated over a 4-year period at our center. The rate of intracranial hemorrhage (ICH), discharge modified Rankin Scale (mRS) score, and mortality at 3 months were compared between groups, according to accuracy of the dose of tPA., Results: We found that 140 of 164 (85%) acute ischemic stroke patients treated with tPA had a measured weight documented in the chart after treatment. Of these, 13 patients received ≥1.0 mg/kg and 16 patients received ≤0.8 mg/kg, based on a comparison of the weight used for the tPA dose calculation and the subsequent measured weight. Four of 13 (31%) patients treated with ≥1.0 mg/kg of tPA developed ICH. Patients who inadvertently received higher doses of tPA had a lower likelihood of a good functional outcome at discharge (mRS score 0-2; 0% v 34%; P = .009). No difference in 3-month mortality was observed, although patients who were not weighed in hospital had a threefold increase in discharge mortality (21% v 7%; P = .019)., Conclusions: Our findings provide support for the practice of accurately weighing all acute ischemic stroke patients before thrombolysis., (Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.)