Tuberculosis Treatment Initiation Research Articles

Patient characteristics and predictors of mortality among children hospitalised with tuberculosis: A six-year case series study in Uganda.

The high case-fatality rates among children with tuberculosis (TB) are reportedly driven by in-hospital mortality and severe forms of TB. Therefore, there is need to better understand the predictors of mortality among children hospitalised with TB. We examined the patient clinical profiles, length of hospital stay from date of admission to date of final admission outcome, and predictors of mortality among children hospitalised with TB at two tertiary hospitals in Uganda. We conducted a case-series study of children below 15 years of age hospitalised with TB, from January 1st, 2016, to December 31st, 2021. Convenience sampling was done to select TB cases from paper-based medical records at Mulago National Referral Hospital (MNRH) in urban Kampala, and Fort Portal Regional Referral Hospital (FRRH) in rural Fort Portal. We fitted linear and logistic regression models with length of stay and in-hospital mortality as key outcomes. Out of the 201 children hospitalised with TB, 50 were at FRRH, and 151 at MNRH. The male to female ratio was 1.5 with median age of 2.6 years (Interquartile range-IQR 1-6). There was a high prevalence of HIV (67/171, 39%), severe malnutrition reported as weight-for-age Z-score <-3SD (51/168, 30%). Among children with pulmonary TB who initiated anti-tuberculosis therapy (ATT) either during hospitalisation or within seven days prior to hospitalisation; cough (134/143, 94%), fever (111/143, 78%), and dyspnoea (78/143, 55%) were common symptoms. Children with TB meningitis commonly presented with fever (17/24, 71%), convulsions (14/24 58%), and cough (13/24, 54%). The median length of hospital stay was 8 days (IQR 5-15). Of the 199 children with known in-hospital outcomes, 34 (17.1%) died during hospitalisation. TB meningitis was associated with in-hospital mortality (aOR = 3.50, 95% CI = 1.10-11.17, p = 0.035), while male sex was associated with reduced mortality (aOR = 0.33, 95% CI = 0.12-0.95, p = 0.035). Hospitalisation in the urban hospital predicted a 0.48-day increase in natural log-transformed length of hospital stay (ln-length of stay) (95% CI 0.15-0.82, p = 0.005), but not age, sex, HIV, malnutrition, or TB meningitis. In-hospital mortality was high, and significantly driven almost four times higher by TB meningitis, with longer hospital stay among children in urban hospitals. The high in-hospital mortality and long hospital stay may be reduced by timely TB diagnosis and treatment initiation among children.

QMAC-DST for Rapid Detection of Drug Resistance in Pulmonary Tuberculosis Patients: A Multicenter Pre-Post Comparative Study.

Background/Objectives: This study explores the impact of QMAC-DST, a rapid, fully automated phenotypic drug susceptibility test (pDST), on the treatment of tuberculosis (TB) patients. Methods: This pre-post comparative study, respectively, included pulmonary TB patients who began TB treatment between 1 December 2020 and 31 October 2021 (pre-period; pDST using the Löwenstein-Jensen (LJ) DST (M-kit DST)) and between 1 November 2021 and 30 September 2022 (post-period; pDST using the QMAC-DST) in five university-affiliated tertiary care hospitals in South Korea. We compared the turnaround times (TATs) of pDSTs and the time to appropriate treatment for patients whose anti-TB drugs were changed based on these tests between the groups. All patients were permitted to use molecular DSTs (mDSTs). Results: A total of 182 patients (135 in the M-kit DST group and 47 in the QMAC-DST group) were included. The median TAT was 36 days for M-kit DST (interquartile range (IQR), 30-39) and 12 days for QMAC-DST (IQR, 9-15), with the latter being significantly shorter (p < 0.001). Of the total patients, 10 (5.5%) changed their anti-TB drugs based on the mDST or pDST results after initiating TB treatment (8 in the M-kit DST group and 2 in the QMAC-DST group). In the M-kit DST group, three (37.5%) patients changed anti-TB drugs based on the pDST results. In the QMAC-DST group, all changes were due to mDST results; therefore, calculating the time to appropriate treatment for patients whose anti-TB drugs were changed based on pDST results was not feasible. In the QMAC-DST group, 46.8% of patients underwent the first-line line probe assay compared to 100.0% in the M-kit DST group (p < 0.001), indicating that rapid QMAC-DST results provide quicker assurance of the ongoing treatment by confirming susceptibility to the current anti-TB drugs. Conclusions: QMAC-DST delivers pDST results more rapidly than LJ-DST, ensuring faster confirmation for the current treatment regimen.

Enhanced tuberculosis diagnosis with computer-aided chest X-ray and urine LAM in adults with HIV admitted to hospital (CASTLE study): A cluster randomised trial.

People with HIV (PHIV) admitted to hospital have high mortality, with tuberculosis (TB) being the major cause of death. Systematic use of new TB diagnostics could improve TB diagnosis and might improve outcomes. We conducted a cluster randomised trial among adult PHIV admitted to Zomba Central Hospital, Malawi. Admission-days were randomly assigned to: enhanced TB diagnostics using urine lipoarabinomannan (LAM) antigen tests (SILVAMP-LAM, Fujifilm, Japan and Determine-LAM, Alere/Abbot, USA), digital chest X-ray with computer aided diagnosis (dCXR-CAD, CAD4TBv6, Delft, Netherlands), plus usual care ("enhanced TB diagnostics"); or usual care alone ("usual care"). The primary outcome was TB treatment initiation during admission. Secondary outcomes were 56-day mortality, TB diagnosis within 24-hours, and undiagnosed TB at discharge, ascertained by culture of one admission sputum sample. Between 2 September 2020 and 15 February 2022, we recruited 419 people. Four people were excluded post-recruitment, leaving 415 adults recruited during 207 randomly assigned admission-days in modified intention-to-treat analysis. At admission, 90.8% (377/415) were taking antiretroviral therapy (ART) with median (IQR) CD4 cell count 240 cells/mm3. In the enhanced diagnostic arm, median CAD4TBv6 score was 60 (IQR: 51-71), 4.4% (9/207) had SILVAMP-LAM-positive and 14.4% (29/201) had Determine-LAM positive urine with three samples positive by both urine tests. TB treatment was initiated in 46/208 (22%) in enhanced TB diagnostics arm and 24/207 (12%) in usual care arm (risk ratio [RR] 1.92, 95% CI 1.20-3.08). There was no difference in mortality by 56 days (enhanced TB diagnosis: 54/208, 26%; usual care: 52/207, 25%; hazard ratio 1.05, 95% CI 0.72-1.53); TB treatment initiation within 24 hours (enhanced TB diagnosis: 8/207, 3.9%; usual care: 5/208, 2.4%; RR 1.61, 95% CI 0.53-4.71); or undiagnosed microbiological-confirmed TB at discharge (enhanced TB diagnosis, 0/207 (0.0%), usual care arm 2/208 (1.0%) (p = 0.50). Urine SILVAMP-LAM/Determine-LAM plus dCXR-CAD diagnostics identified more hospitalised PHIV with TB than usual care. The increase in TB treatment appeared mainly due to greater use of Determine-LAM, rather than SILVAMP-LAM or dCXR-CAD. Poor concordance between Determine-LAM and SILVAMP-LAM urine tests requires further investigation. Inpatient mortality for adults with HIV remains unacceptability high.

Testing novel strategies for patients hospitalised with HIV-associated disseminated tuberculosis (NewStrat-TB): protocol for a randomised controlled trial

BackgroundHIV-associated tuberculosis (TB) contributes disproportionately to global tuberculosis mortality. Patients hospitalised at the time of the diagnosis of HIV-associated disseminated TB are typically severely ill and have a high mortality risk despite initiation of tuberculosis treatment. The objective of the study is to assess the safety and efficacy of both intensified TB treatment (high dose rifampicin plus levofloxacin) and immunomodulation with corticosteroids as interventions to reduce early mortality in hospitalised patients with HIV-associated disseminated TB.MethodsThis is a phase III randomised controlled superiority trial, evaluating two interventions in a 2 × 2 factorial design: (1) high dose rifampicin (35 mg/kg/day) plus levofloxacin added to standard TB treatment for the first 14 days versus standard tuberculosis treatment and (2) adjunctive corticosteroids (prednisone 1.5 mg/kg/day) versus identical placebo for the first 14 days of TB treatment. The study population is HIV-positive patients diagnosed with disseminated TB (defined as being positive by at least one of the following assays: urine Alere LAM, urine Xpert MTB/RIF Ultra or blood Xpert MTB/RIF Ultra) during a hospital admission. The primary endpoint is all-cause mortality at 12 weeks comparing, first, patients receiving intensified TB treatment to standard of care and, second, patients receiving corticosteroids to those receiving placebo. Analysis of the primary endpoint will be by intention to treat. Secondary endpoints include all-cause mortality at 2 and 24 weeks. Safety and tolerability endpoints include hepatoxicity evaluations and corticosteroid-related adverse events.DiscussionDisseminated TB is characterised by a high mycobacterial load and patients are often critically ill at presentation, with features of sepsis, which carries a high mortality risk. Interventions that reduce this high mycobacterial load or modulate associated immune activation could potentially reduce mortality. If found to be safe and effective, the interventions being evaluated in this trial could be easily implemented in clinical practice.Trial registrationClinicalTrials.gov NCT04951986. Registered on 7 July 2021https://clinicaltrials.gov/study/NCT04951986

Rapid decrease in IL-1Ra and IP-10 plasma levels following tuberculosis treatment initiation

ObjectivesMonitoring tools that could provide quick predictions of tuberculosis (TB) treatment outcomes are urgently needed. Here, we assessed whether the evolution of selected biomarkers of innate immunity may help monitoring TB treatment response within 2 weeks of treatment initiation. MethodsANRS12394-LILAC-TB was a proof-of concept prospective study: HIV-negative and HIV-infected adults with a rifampicin-susceptible TB, documented by a positive Xpert MTB/RIF test, were enrolled in Cambodia and Côte d'Ivoire. Plasma concentrations of IL-1Ra, IP-10 and sCD163 were measured by commercial ELISA kits. A Wilcoxon test for paired data was used for longitudinal comparisons. Results55 patients were enrolled (women: 31%, median age: 37 years; median CD4 count in the 10/13 HIV-infected participants: 53 cells/mm3). Overall, 83% were considered in TB treatment success. Compared to baseline, IL-1Ra plasma levels significantly decreased as soon as Week (W)1, independently of HIV status (-71% in HIV-positive vs. -33% in HIV-negative; p<0.001). IP-10 plasma levels significantly decreased at W1 and W2 compared to baseline (p<0.0001), but that decrease was less marked in HIV-infected participants. ConclusionOur findings suggest that measuring IL-1Ra plasma levels with a standard ELISA technique at baseline then one week after TB treatment onset could help clinicians to quickly assess TB treatment response.

Causes of Late Diagnosis of Tuberculosis in HIV Patients

The objective: to determine causes of frequent detection of disseminated tuberculosis in HIV-infected patients taking into account the behavioral characteristics of patients, to propose additional measures to enhance tuberculosis detection.Subjects and Methods. 108 questionnaires filled out by TB/HIV co-infected patients staying in specialized hospitals in 3 regions of the Russian Federation were studied. We filled out the first 18 questionnaires ourselves while talking to patients, to assess whether the questions were clear to patients. The questionnaire included 28 questions with prompted answers; in addition, patients could give their own answers. Using the questionnaire, we found out whether the patients were seeking medical help in a timely manner, units to which they referred, awareness of tuberculosis before developing it, and exposure to tuberculous infection.Results. The majority of interviewed patients with previously diagnosed HIV infection did not undergo medical examination at the Center for AIDS Prevention and Control (CAIDSPC). When complaints associated with tuberculosis appeared, 57/108 (52.8%) respondents referred to the clinic at their place of residence. In 56/108 (51.8%) patients, 2 or more months passed from the moment of referral for medical help to diagnosis and initiation of tuberculosis treatment. 7/108 (6.5%) respondents reported history of tuberculosis, and 4/108 (3.7%) respondents reported exposure to a tuberculosis patient. After developing tuberculosis, 20/108 (18.5%) respondents were exposed to other HIV-infected patients. After detection of HIV infection, 93 (86.1%) patients indicated that they had not been made aware of tuberculosis.

Exploring health care providers’ engagement in prevention and management of multidrug resistant Tuberculosis and its factors in Hadiya Zone health care facilities: qualitative study

BackgroundEngagement of healthcare providers is one of the World Health Organization strategies devised for prevention and provision of patient centered care for multidrug resistant tuberculosis. The need for current research question rose because of the gaps in evidence on health professional’s engagement and its factors in multidrug resistant tuberculosis service delivery as per the protocol in the prevention and management of multidrug resistant tuberculosis.PurposeThe purpose of this study was to explore the level of health care providers’ engagement in multidrug resistant tuberculosis prevention and management and influencing factors in Hadiya Zone health facilities, Southern Ethiopia.MethodsDescriptive phenomenological qualitative study design was employed between 02 May and 09 May, 2019. We conducted a key informant interview and focus group discussions using purposely selected healthcare experts working as directly observed treatment short course providers in multidrug resistant tuberculosis treatment initiation centers, program managers, and focal persons. Verbatim transcripts were translated to English and exported to open code 4.02 for line-by-line coding and categorization of meanings into same emergent themes. Thematic analysis was conducted based on predefined themes for multidrug resistant tuberculosis prevention and management and core findings under each theme were supported by domain summaries in our final interpretation of the results. To maintain the rigors, Lincoln and Guba’s parallel quality criteria of trustworthiness was used particularly, credibility, dependability, transferability, confirmability and reflexivity.ResultsTotal of 26 service providers, program managers, and focal persons were participated through four focus group discussion and five key informant interviews. The study explored factors for engagement of health care providers in the prevention and management of multidrug resistant tuberculosis in five emergent themes such as patients’ causes, perceived susceptibility, seeking support, professional incompetence and poor linkage of the health care facilities. Our findings also suggest that service providers require additional training, particularly in programmatic management of drug-resistant tuberculosis.ConclusionThe study explored five emergent themes: patient’s underlying causes, seeking support, perceived susceptibility, professionals’ incompetence and health facilities poor linkage. Community awareness creation to avoid fear of discrimination through provision of support for those with multidrug resistant tuberculosis is expected from health care providers using social behavioral change communication strategies. Furthermore, program managers need to follow the recommendations of World Health Organization for engaging healthcare professionals in the prevention and management of multidrug resistant tuberculosis and cascade trainings in clinical programmatic management of the disease for healthcare professionals.

Systems analysis and improvement approach to optimize tuberculosis (SAIA-TB) screening, treatment, and prevention in South Africa: a stepped-wedge cluster randomized trial

BackgroundThe use of systems engineering tools, including the development and use of care cascades using routinely collected data, process mapping, and continuous quality improvement, is used for frontline healthcare workers to devise systems level change. South Africa experiences high rates of tuberculosis (TB) infection and disease as well as HIV co-infection. The Department of Health has made significant gains in HIV services over the last two decades, reaching their set “90–90-90” targets for HIV. However, TB services, although robust, have lagged in comparison for both disease and infection. The Systems Analysis and Improvement Approach (SAIA) is a five-step implementation science method, drawn from systems engineering, to identify, define, and implement workflow modifications using cascade analysis, process mapping, and repeated quality improvement cycles within healthcare facilities.MethodsThis stepped-wedge cluster randomized trial will evaluate the effectiveness of SAIA on TB (SAIA-TB) cascade optimization for patients with TB and high-risk contacts across 16 clinics in four local municipalities in the Sarah Baartman district, Eastern Cape, South Africa. We hypothesize that SAIA-TB implementation will lead to a 20% increase in each of: TB screening, TB preventive treatment initiation, and TB disease treatment initiation during the 18-month intervention period. Focus group discussions and key informant interviews with clinic staff will also be conducted to determine drivers of implementation variability across clinics.DiscussionThis study has the potential to improve TB screening, treatment initiation, and completion for both active disease and preventive measures among individuals with and without HIV in a high burden setting. SAIA-TB provides frontline health care workers with a systems-level view of their care delivery system with the aim of sustainable systems-level improvements.Trial registrationClinicaltrials.gov, NCT06314386. Registered 18 March 2024, https://clinicaltrials.gov/study/NCT06314386. NCT06314386.

Programmatic implementation of depression screening and remote mental health support sessions for persons recently diagnosed with TB in Lima, Peru during the COVID-19 pandemic

Programmatic implementation of depression screening and remote mental health support sessions for persons recently diagnosed with TB in Lima, Peru during the COVID-19 pandemic

IJCM_223A: Assessment of the Tuberculosis Surveillance System in Amethi district of Uttar Pradesh, India, 2023

Background: Tuberculosis (TB) continues to be one of the leading global causes of death. In 2022, globally 10.6 million TB cases were estimated, 28% from India. Uttar Pradesh (UP) has TB incidence rate of 210 per 100,000 population. Amethi district has a population of 21 lakhs and 10 TB units. We assessed the TB surveillance system in Amethi for its attributes and to provide recommendations for improvement. Objective: To describe and evaluate tuberculosis surveillance system in Amethi (UP) Recommendation to strengthen TB surveillance system. Methodology: We evaluated the timeliness and completeness of surveillance data of Amethi from the January to June 2023 through the online Nikshay portal. We assessed the timeliness for treatment started within three days of diagnosis and flow of monthly reports at every level. We assessed the data quality by completeness of information of the enrolled patients. We interviewed the Frontline Health Workers (FLW) from each blocks as per their availability during the time of filed visit regarding the knowledge about TB, symptoms, modes of spread and treatment selected. Results: Nikshay portal data had 1500 patient entries for Amethi during Jan- June 2023. The median age of the patients was 37 (range: Conclusion: The Amethi TB surveillance has a good timeliness and completeness in initiating TB treatment to those diagnosed; however, requires improvement for health workers awareness and reporting in the blocks. We recommended district to conduct yearly capacity building of FLW and conduct monthly review.

Aerosolization of viable Mycobacterium tuberculosis bacilli by tuberculosis clinic attendees independent of sputum-Xpert Ultra status

Potential Mycobacterium tuberculosis (Mtb) transmission during different pulmonary tuberculosis (TB) disease states is poorly understood. We quantified viable aerosolized Mtb from TB clinic attendees following diagnosis and through six months' follow-up thereafter. Presumptive TB patients (n=102) were classified by laboratory, radiological, and clinical features into Group A: Sputum-Xpert Ultra-positive TB (n=52), Group B: Sputum-Xpert Ultra-negative TB (n=20), or Group C: TB undiagnosed (n=30). All groups were assessed for Mtb bioaerosol release at baseline, and subsequently at 2 wk, 2 mo, and 6 mo. Groups A and B were notified to the national TB program and received standard anti-TB chemotherapy; Mtb was isolated from 92% and 90% at presentation, 87% and 74% at 2 wk, 54% and 44% at 2 mo and 32% and 20% at 6 mo, respectively. Surprisingly, similar numbers were detected in Group C not initiating TB treatment: 93%, 70%, 48% and 22% at the same timepoints. A temporal association was observed between Mtb bioaerosol release and TB symptoms in all three groups. Persistence of Mtb bioaerosol positivity was observed in ~30% of participants irrespective of TB chemotherapy. Captured Mtb bacilli were predominantly acid-fast stain-negative and poorly culturable; however, three bioaerosol samples yielded sufficient biomass following culture for whole-genome sequencing, revealing two different Mtb lineages. Detection of viable aerosolized Mtb in clinic attendees, independent of TB diagnosis, suggests that unidentified Mtb transmitters might contribute a significant attributable proportion of community exposure. Additional longitudinal studies with sputum culture-positive and -negative control participants are required to investigate this possibility.

Performance of a stool-based quantitative PCR assay for the diagnosis of tuberculosis in adolescents and adults: a multinational, prospective diagnostic accuracy study

Despite increasing availability of rapid molecular tests for the diagnosis of tuberculosis in high-burden settings, many people with tuberculosis are undiagnosed. Reliance on sputum as the primary specimen for tuberculosis diagnostics contributes to this diagnostic gap. We evaluated the diagnostic accuracy and additive yield of a novel stool quantitative PCR (qPCR) assay for the diagnosis of tuberculosis in three countries in Africa with high tuberculosis burdens. We undertook a prospective diagnostic accuracy study in Eswatini, Mozambique, and Tanzania from Sept21, 2020, to Feb 2, 2023, to compare the diagnostic accuracy for tuberculosis of a novel stool qPCR test with the current diagnostic standard for Mycobacterium tuberculosis DNA detection from sputum and stool, Xpert-MTB/RIF Ultra (Xpert Ultra). Sputum, stool, and urine samples were provided by a cohort of participants, aged 10 years or older, diagnosed with tuberculosis. Participants with tuberculosis (cases) were enrolled within 72 h of treatment initiation for tuberculosis diagnosed clinically or following laboratory confirmation. Participants without tuberculosis (controls) consisted of household contacts of the cases who did not develop tuberculosis during a 6-month follow-up. The performance was compared with a robust composite microbiological reference standard (CMRS). The cohort of adolescents and adults (n=408) included 268 participants with confirmed or clinical tuberculosis (cases), 147 (55%) of whom were living with HIV, and 140 participants (controls) without tuberculosis. The sensitivity of the novel stool qPCR was 93·7% (95% CI 87·4-97·4) compared with participants with detectable growth on M tuberculosis culture, and 88·1% (81·3-93·0) compared with sputum Xpert Ultra. The stool qPCR had an equivalent sensitivity as sputum Xpert Ultra (94·8%, 89·1-98·1) compared with culture. Compared with the CMRS, the sensitivity of the stool qPCR was higher than the current standard for tuberculosis diagnostics on stool, Xpert Ultra (80·4%, 73·4-86·2 vs 73·5%, 66·0-80·1; p=0·025 on paired comparison). The qPCR also identified 17-21% additional tuberculosis cases compared to sputum Xpert Ultra or sputum culture. In controls without tuberculosis, the specificity of the stool qPCR was 96·9% (92·2-99·1). In this study, a novel qPCR for the diagnosis of tuberculosis from stool specimens had a higher accuracy in adolescents and adults than the current diagnostic PCR gold standard on stool, Xpert-MTB/RIF Ultra, and equivalent sensitivity to Xpert-MTB/RIF Ultra on sputum. National Institutes of Health (NIH) Allergy and Infectious Diseases, and NIH Fogarty International Center.

GeneXpert MTB/RIF Ultra vs Unstimulated Interferon γ (IRISA-TB) for the Diagnosis of Tuberculous Pericarditis in a Tuberculosis-Endemic Setting.

Tuberculous pericarditis (TBP) is a paucibacillary disease, where host biomarkers such as unstimulated interferon γ (IRISA-TB) have high diagnostic accuracy. However, DNA-based diagnostic tests (GeneXpert Ultra), more sensitive than an earlier versions, have recently become available. Given that the diagnosis of TBP is challenging, we performed a comparative diagnostic accuracy study comparing both assays. We recruited 99 consecutive patients with suspected TBP in Cape Town, South Africa. Definite TBP was defined by microbiological confirmation of tuberculosis (TB) on pericardial fluid culture or an alternative polymerase chain reaction-based test (GeneXpert MTB/RIF) or by use of sputum (polymerase chain reaction or culture). Probable TBP was defined as a high clinical suspicion of TB accompanied by anti-TB treatment, while non-TBP was defined as negative microbiological test results for TB without initiation of TB treatment and/or the presence of an alternative diagnosis. There were 39 patients with definite TBP, 35 with probable TBP, and 23 with non-TBP. Approximately 70% of participants who received TB treatment were HIV coinfected. Overall, IRISA-TB was more sensitive than Xpert Ultra (88.6% [95% CI, 74.1%-95.5%] vs 71.5% [55.0%-83.7%], n = 53) and significantly more sensitive in participants who were HIV uninfected (100% [95% CI, 72.3%-100.0%] vs 60% [31.3%-83.2%], P = .03). In patients with definite and probable TBP combined (n = 84), sensitivity was significantly higher with IRISA-TB (77.3% [95% CI, 65.9%-85.8%] vs 37.9 [27.2%-50.0%], P < .0001). A similar pattern was seen in persons who were HIV uninfected (88.3% vs 35.3%, P = .002). Specificity was high for both assays (>95%). Unstimulated interferon γ (IRISA-TB) was significantly more sensitive than Xpert Ultra for the diagnosis of TB pericarditis in a TB-endemic resource-poor setting.

Delay in seeking treatment and associated factors among pulmonary tuberculosis patients attending public health facilities in the Metekel zone, Benishangul Gumuz region, Western Ethiopia.

Tuberculosis is a major global public health problem and a leading cause of morbidity and mortality in Ethiopia. TB prevention and control in low-income countries, such as Ethiopia, face significant challenges, including late detection and treatment initiation. A delay in the initiation of tuberculosis treatment increases the morbidity and mortality of patients and community transmission. Therefore, this study aimed to assess patient delay and associated factors among pulmonary tuberculosis patients attending public health facilities in the Metekel Zone, Benishangul Gumuz Region, Western Ethiopia. An institution-based cross-sectional study was conducted from March to August 2020 among newly diagnosed pulmonary tuberculosis patients. All pulmonary tuberculosis patients (416) who came to all public health facilities of the Metekel zone for treatment during the period were included. Data were collected through face-to-face interviews using a structured and pretested questionnaire. A multivariable logistic regression was fitted to identify independent factors for delay in seeking treatment among PTB patients. Adjusted odds ratios with 95% CIs were determined, and variables with p values <0.05 were considered statistically significant. Nearly three-fourths 302 (72.6, 95% CI: 68.5, 76.7) of the patients were delayed in seeking medical advice, with a median patient delay of 27 days (IQR: 21-31). Age of the patients [above 54 years (AOR = 2.65, 95% CI: 1.30, 5.40), 36-54 years (AOR = 1.86, 95% CI: 1.14,3.02)], family size of 5 members and above (AOR = 1.62, 95% CI: 1.10-3.14), travel time above 60 min (AOR = 3.65, 95% CI: 1.55, 8.60), history of visits to informal care providers (AOR = 1.74, 95% CI: 1.11, 3.14), and poor knowledge about PTB (AOR = 1.64, 95% CI: 1.04-2.44) were statistically significant factors associated with delays in seeking treatment among PTB patients. Most pulmonary tuberculosis patients delay seeking medical advice for their illnesses. Delays in seeking treatment were associated with older age, large household size, longer travel time to reach the nearby health facility, visiting informal care providers, and poor knowledge about pulmonary tuberculosis. Hence, it is crucial to consider community screening programs, enhance public awareness, and ensure the accessibility of TB diagnostic and treatment services.

Iterative evaluation of mobile computer-assisted digital chest x-ray screening for TB improves efficiency, yield, and outcomes in Nigeria.

Wellness on Wheels (WoW) is a model of mobile systematic tuberculosis (TB) screening of high-risk populations combining digital chest radiography with computer-aided automated detection (CAD) and chronic cough screening to identify presumptive TB clients in communities, health facilities, and prisons in Nigeria. The model evolves to address technical, political, and sustainability challenges. Screening methods were iteratively refined to balance TB yield and feasibility across heterogeneous populations. Performance metrics were compared over time. Screening volumes, risk mix, number needed to screen (NNS), number needed to test (NNT), sample loss, TB treatment initiation and outcomes. Efforts to mitigate losses along the diagnostic cascade were tracked. Persons with high CAD4TB score (≥80), who tested negative on a single spot GeneXpert were followed-up to assess TB status at six months. An experimental calibration method achieved a viable CAD threshold for testing. High risk groups and key stakeholders were engaged. Operations evolved in real time to fix problems. Incremental improvements in mean client volumes (128 to 140/day), target group inclusion (92% to 93%), on-site testing (84% to 86%), TB treatment initiation (87% to 91%), and TB treatment success (71% to 85%) were recorded. Attention to those as highest risk boosted efficiency (the NNT declined from 8.2 ± SD8.2 to 7.6 ± SD7.7). Clinical diagnosis was added after follow-up among those with ≥ 80 CAD scores and initially spot -sputum negative found 11 additional TB cases (6.3%) after 121 person-years of follow-up. Iterative adaptation in response to performance metrics foster feasible, acceptable, and efficient TB case-finding in Nigeria. High CAD scores can identify subclinical TB and those at risk of progression to bacteriologically-confirmed TB disease in the near term.

Delays in Diagnosis and Treatment of Pulmonary Tuberculosis Patients during the COVID-19 Pandemic in Dushanbe, Tajikistan, 2022

The objective: to study delays in provision of medical care to pulmonary tuberculosis patients above 15 years old with laboratory confirmation of the diagnosis before and during the COVID-19 pandemic in Dushanbe, Tajikistan.Subjects and Methods. A retrospective cohort study was conducted among new pulmonary tuberculosis patients above 15 years old with laboratory confirmation of the diagnosis registered by TB Control Centers in Dushanbe in 2019–2021. Information was collected from medical records, medical databases, and patient questionnaires. Two types of delays were detected during the provision of medical care: delays related to the patient (defined as &gt;14 days between onset of tuberculosis symptoms and the first visit to a health unit); delays related to health system (defined as &gt;3 days from the first visit to TB unit to the initiation of tuberculosis treatment).Results. Of the 472 patients enrolled in the study, 276 were registered during the COVID-19 pandemic (2020–2021) and 196 patients were registered before the pandemic (2019). Frequency of delays was similar (83% vs 82%, p=0.8) during and before the COVID-19 pandemic. The frequency of delay related to health system was statistically significantly lower during the pandemic versus the period before the pandemic (34% vs 44%, p=0.023). The median duration of delays associated to the patient before the pandemic (60 days, IQR: 15–541) and during the pandemic (60 days, IQR: 15–360, р=0.6) was also similar as well as delays related to health system (before the pandemic – 7 days, IQR: 4–336) and during the pandemic (7 days, IQR: 4–225, р=0.6).Conclusion. Contrary to the expected result, no significant difference in delays related to the patient before and during the pandemic was found, and the frequency of delay related to health system during the pandemic significantly reduced compared to the period before the pandemic.

Risk factors in the delay of treatment of childhood tuberculosis in a Peruvian Hospital

To determine the risk factors associated with delayed initiation of tuberculosis (TB) treatment in children under 15 years of age. Case-control study. Patients <15 years of age with a diagnosis of childhood pulmonary tuberculosis (c-PTB) with delayed treatment initiation >24 hours were included. Clinical and epidemiological variables were evaluated: age, gender, guardian's education, poverty level, origin, family history of TB, altered imaging findings, symptomatic, PPD >10mm, histology, bacteriology, resistance to treatment, and healthcare network. Bi and multivariate logistic regression analysis was performed, through which odds ratios were calculated. We evaluated 116 patients with c-PTB with a delayed initiation of specific treatment of more than 24 hours, and 264 with start of treatment in the first 24 hours. The delay in anti-tuberculosis treatment had a median of 3 days with an interquartile range of 2 to 7 days. The patient with the least educated guardian had a delay in treatment initiation with an odds ratio of 7.47 (95%CI: 4.13 - 13.52). Belonging to the healthcare network A of Callao decreased the probability of having tuberculosis by 0.224 times (95%CI:0.11 - 0.46). Incomplete education level of the guardian is a risk factor associated with delayed initiation of c-PTB treatment in children under 15 years of age while belonging to the Callao healthcare network A is a factor that decreases the risk in the group under study.

1883. Features and Outcomes of Tuberculosis in Documented versus Undocumented Migrants in Israel

Abstract Background In countries with low tuberculosis (TB) incidence, most TB cases are observed in foreign-born individuals, including permanent immigrants, and undocumented migrants. There is limited information regarding the differences within these groups. In Israel, where TB prevalence is &amp;lt; 2 cases/100,000 persons, 85% of TB cases occur in foreign-born people. We examined risk factors, clinical course, and outcomes between documented and undocumented immigrants hospitalized with active TB. Methods A retrospective analysis of medical records from foreign-born active TB patients admitted to a 700-bed hospital in the center of Israel between January 1st, 2019, to March 31st, 2023. We included patients who initiated TB treatment during hospitalization and were discharged by April 2023. Undocumented migrants were defined as non-Israeli citizens without medical insurance. We summarized their clinical characteristics, course, and outcomes. Results 48 patients were included, 21 (43.8%) were undocumented migrants. Undocumented migrants were younger (mean age 40.9 vs. 53.0 years, P&amp;lt; 0.001) and predominantly arrived from Africa (95.2% vs. 29.6%, P&amp;lt; 0.001). The prevalence of HIV was similar between both groups. Presenting symptoms, duration of symptoms before admission, rates of bilateral and cavitary pulmonary disease, and extrapulmonary disease were comparable. Multi-drug resistant TB was rare (0% vs. 11.5%, P=0.242). Among patients with positive sputum smears and follow-up, undocumented migrants experienced a longer time to achieve negative sputum cultures (76.0 days vs. 36.8 days, P=0.004), and hospitalizations lasting over 30 days were also more common among undocumented migrants (71.4% vs. 40.7%, P=0.045). Multivariate analysis identified undocumented migrant status, thrombocytosis, and bilateral and cavitary pulmonary disease as risk factors for prolonged hospitalization. Conclusion Although the clinical features of TB were similar between documented and undocumented migrants, the response to treatment was slower, and hospital stays were longer among undocumented migrants. This may be due to undocumented migrants presenting with more advanced disease or lack of suitable conditions for isolation and treatment at home. Disclosures Yasmin Maor, MD, Astra Zeneca: Advisor/Consultant|Astra Zeneca: Honoraria|Gilead: Honoraria|GSK: Honoraria|kamada: Honoraria|Medison: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Grant/Research Support|Pfizer: Honoraria

TB NOTIFICATION IN CHILDREN: THE EXPERIENCE OF TARGETED COMMUNITY DEMAND CREATION AMIDST INSECURITY IN IMO STATE, NIGERIA

This paper explores the challenges and successes of tuberculosis (TB) notification in children amidst a backdrop of insecurity in Imo State, Nigeria. Emphasizing targeted community demand creation strategies, the study investigates the intricate relationship between insecurity, community engagement, and pediatric TB detection. Drawing upon a comprehensive literature review, this research delves into the epidemiology, diagnosis, and treatment of TB in children, the ramifications of insecurity on healthcare access in Imo State, and effective community engagement strategies in healthcare initiatives. The literature findings underscore the substantial burden of TB among children and the distinct hurdles faced in environments characterized by insecurity. The prevailing insecurity in Imo State significantly disrupts healthcare services, leading to delays in TB diagnosis and treatment initiation. Nevertheless, the review identifies community engagement approaches as a promising avenue for bolstering TB notification rates in pediatric populations. These approaches empower local communities to actively participate in the identification and management of TB cases, ultimately contributing to the enhancement of pediatric TB notification. A conceptual framework, derived from amalgamated literature, elucidates the intricate interplay between insecurity, community engagement, and TB notification. This study highlights the pivotal role of community-driven interventions in mitigating the challenges posed by insecurity in Imo State, Nigeria, and presents actionable recommendations for the development of healthcare policies and programs tailored to the region. This research not only augments our comprehension of TB notification among children within insecure contexts but also provides valuable insights into the broader domain of community-based healthcare interventions. It underscores the exigency for customized strategies to address TB in pediatric populations in regions marked by insecurity, ultimately contributing to the amelioration of health outcomes for children in Imo State, Nigeria, and analogous settings&#x0D; Keywords: TB, Children, Community, Nigeria.

Perinatal tuberculosis-An approach to an under-recognized diagnosis.

Tuberculosis (TB) in young infants (<3 months of age), often referred to as perinatal TB, is underdiagnosed, leading to severe morbidity and high mortality. Perinatal TB includes both congenital and postnatal transmission of Mycobacterium tuberculosis. We aimed to increase an awareness of TB in neonates and young infants and to provide guidance on the assessment and management when in contact with mothers with TB during or soon after pregnancy. Approximately 217,000 pregnant women develop TB annually; if they are not diagnosed and treated during pregnancy, their infants are at high risk of adverse birth outcomes and TB disease. Although safe and effective antituberculosis treatment regimens are available during pregnancy, the diagnosis of TB is challenging. Infants born to mothers newly diagnosed with TB, not receiving any effective treatment or with cultures not yet negative, should be assessed for TB disease or M. tuberculosis infection. TB preventive therapy should be instituted if the infant is clinically well but exposed to TB, while prompt initiation of TB treatment is essential if TB disease is presumed. HIV status of mother and infant should be considered as this will affect the management. Further research is needed for the diagnosis and prevention of TB during pregnancy, an early diagnosis of TB in infants, and antituberculosis drug pharmacokinetics in young infants.