Granulomatous meningoencephalitis and blindness associated with Mycobacterium tuberculosis complex infection in a senile female chimpanzee (Pan troglodytes).

A 40-year old female chimpanzee (Pan troglodytes) developed hyporexia, weight loss, followed by progressive and complete blindness. Tomography demonstrated an intracranial mass in the rostroventral brain involving the optic chiasm, with a presumptive diagnosis of neoplasm. However, histopathology revealed a granulomatous meningoencephalitis, and tissue samples tested positive for Mycobacterium tuberculosis.

Tuberculosis in southern Morocco: Retrospective analysis from 2006 to 2012.

INTRODUCTION: Tuberculosis, a global major concern, causes millions of deaths annually despite WHO strategies. A persistent gap in detection and treatment facilitates rapid spread in high-burden countries. AIMS: Analyze the clinical-epidemiological profile of tuberculosis patients in Laayoune and Tarfaya, Morocco, emphasizing risk factors and evolution of the tuberculosis Methods: Retrospective analysis of 1332 tuberculosis cases at the Respiratory Diseases Diagnosis and Treatment Center in Laayoune (2006-2012). Variables with P < 0.10 in univariate analysis were included in multivariate analysis using multiple logistic regression to define the risk factors for tuberculosis, expressed as odds ratios (OR) with a 95% confidence interval (CI). RESULTS: The analysis revealed a pulmonary predominance (≈61%), with pleural (41.3%) and lymph node (31.5%) tuberculosis prevalent among extrapulmonary cases. Among 515 extrapulmonary tuberculosis cases, intestinal tuberculosis (14 cases) showed the highest mortality rate at 14.29%. The 15 to 64 age groups had a significantly higher risk of contracting pulmonary tuberculosis to children, and the 65 and over age group also had the highest risk of developing pulmonary tuberculosis (aOR=5.83 [2.43, 14.00]). Other risk factors included rural origin, personal history of tuberculosis, and smoking, all significantly associated with pulmonary tuberculosis (aOR=2.40 [1.001, 5.76]; aOR=2.00 [1.11, 3.61]; aOR=2.38 [1.40, 4.06]). Conversely, female gender was a protective factor (aOR=0.53 [0.40, 0.70]). Regarding recovery and loss to follow-up rates, they were higher in those with pulmonary tuberculosis (39.0% vs 2.1%; aOR=33.41 [17, 66.52]; 16.9% vs 10.3%; aOR=1.57 [1.02, 2.41], respectively). CONCLUSION: Holistic initiatives across various sectors will be essential to eliminate tuberculosis by 2030.

Prediction of tuberculosis clusters in the riverine municipalities of the Brazilian Amazon with machine learning.

OBJECTIVE: Tuberculosis (TB) is the second most deadly infectious disease globally, posing a significant burden in Brazil and its Amazonian region. This study focused on the "riverine municipalities" and hypothesizes the presence of TB clusters in the area. We also aimed to train a machine learning model to differentiate municipalities classified as hot spots vs. non-hot spots using disease surveillance variables as predictors. METHODS: Data regarding the incidence of TB from 2019 to 2022 in the riverine town was collected from the Brazilian Health Ministry Informatics Department. Moran's I was used to assess global spatial autocorrelation, while the Getis-Ord GI* method was employed to detect high and low-incidence clusters. A Random Forest machine-learning model was trained using surveillance variables related to TB cases to predict hot spots among non-hot spot municipalities. RESULTS: Our analysis revealed distinct geographical clusters with high and low TB incidence following a west-to-east distribution pattern. The Random Forest Classification model utilizes six surveillance variables to predict hot vs. non-hot spots. The machine learning model achieved an Area Under the Receiver Operator Curve (AUC-ROC) of 0.81. CONCLUSION: Municipalities with higher percentages of recurrent cases, deaths due to TB, antibiotic regimen changes, percentage of new cases, and cases with smoking history were the best predictors of hot spots. This prediction method can be leveraged to identify the municipalities at the highest risk of being hot spots for the disease, aiding policymakers with an evidenced-based tool to direct resource allocation for disease control in the riverine municipalities.

Chest Radiograph Screening for Detecting Subclinical Tuberculosis in Asymptomatic Household Contacts, Peru.

The World Health Organization's end TB strategy promotes the use of symptom and chest radiograph screening for tuberculosis (TB) disease. However, asymptomatic early states of TB beyond latent TB infection and active disease can go unrecognized using current screening criteria. We conducted a longitudinal cohort study enrolling household contacts initially free of TB disease and followed them for the occurrence of incident TB over 1 year. Among 1,747 screened contacts, 27 (52%) of the 52 persons in whom TB subsequently developed during follow-up had a baseline abnormal radiograph. Of contacts without TB symptoms, persons with an abnormal radiograph were at higher risk for subsequent TB than persons with an unremarkable radiograph (adjusted hazard ratio 15.62 [95% CI 7.74-31.54]). In young adults, we found a strong linear relationship between radiograph severity and time to TB diagnosis. Our findings suggest chest radiograph screening can extend to detecting early TB states, thereby enabling timely intervention.

Incidence of self-reported tuberculosis treatment with community-wide universal testing and treatment for HIV and tuberculosis screening in Zambia and South Africa: A planned analysis of the HPTN 071 (PopART) cluster-randomised trial.

BACKGROUND: HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach. METHODS AND FINDINGS: HPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value ≤0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time. CONCLUSIONS: In this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01900977.

Community tuberculosis screening, testing and care, Uganda.

Objective: To assess the effectiveness of a community-based tuberculosis and leprosy intervention in which village health teams and health workers conduct door-to-door tuberculosis screening, targeted screenings and contact tracing. Methods: We conducted a before-and-after implementation study in Uganda to assess the effectiveness of the community tuberculosis intervention by looking at reach, outputs, adoption and effectiveness of the intervention. Campaign 1 was conducted in March 2022 and campaign 2 in September 2022. We calculated percentages of targets achieved and compared case notification rates during the intervention with corresponding quarters in the previous year. We also assessed the leprosy screening. Findings: Over 5 days, campaign 1 screened 1 289 213 people (2.9% of the general population), of whom 179 144 (13.9%) fulfilled the presumptive tuberculosis criteria, and 4043 (2.3%) were diagnosed with bacteriologically-confirmed tuberculosis; 3710 (91.8%) individuals were linked to care. In campaign 2, 5 134 056 people (11.6% of the general population) were screened, detecting 428 444 (8.3%) presumptive tuberculosis patients and 8121 (1.9%) bacteriologically-confirmed tuberculosis patients; 5942 individuals (87.1%) were linked to care. The case notification rate increased from 48.1 to 59.5 per 100 000 population in campaign 1, with a case notification rate ratio of 1.24 (95% confidence interval, CI: 1.22-1.26). In campaign 2, the case notification rate increased from 45.0 to 71.6 per 100 000 population, with a case notification rate ratio of 1.59 (95% CI: 1.56-1.62). Of the 176 patients identified with leprosy, 137 (77.8%) initiated treatment. Conclusion: This community tuberculosis screening initiative is effective. However, continuous monitoring and adaptations are needed to overcome context-specific implementation challenges.

Implementation of systematic screening for tuberculosis disease and tuberculosis preventive treatment among people living with HIV attending antiretroviral treatment clinics in Ghana: a national pilot study.

OBJECTIVES: To assess the yield and cost of implementing systematic screening for tuberculosis (TB) disease among people living with HIV (PLHIV) and initiation of TB preventive treatment (TPT) in Ghana. DESIGN: Prospective cohort study from August 2019 to December 2020. SETTING: One hospital from each of Ghana's regions (10 total). PARTICIPANTS: Any PLHIV already receiving or newly initiating antiretroviral treatment were eligible for inclusion. INTERVENTIONS: All participants received TB symptom screening and chest radiography. Those with symptoms and/or an abnormal chest X-ray provided a sputum sample for microbiological testing. All without TB disease were offered TPT. PRIMARY AND SECONDARY OUTCOME MEASURES: We estimated the proportion diagnosed with TB disease and proportion initiating TPT. We used logistic regression to identify factors associated with TB disease diagnosis. We used microcosting to estimate the health system cost per person screened (2020 US$). RESULTS: Of 12 916 PLHIV attending participating clinics, 2639 (20%) were enrolled in the study and screened for TB disease. Overall, 341/2639 (12.9%, 95% CI 11.7% to 14.3%) had TB symptoms and/or an abnormal chest X-ray; 50/2639 (1.9%; 95% CI 1.4% to 2.5%) were diagnosed with TB disease, 20% of which was subclinical. In multivariable analysis, only those newly initiating antiretroviral treatment were at increased odds of TB disease (adjusted OR 4.1, 95% CI 2.0 to 8.2). Among 2589 participants without TB, 2581/2589 (99.7%) initiated TPT. Overall, the average cost per person screened during the study was US$57.32. CONCLUSION: In Ghana, systematic TB disease screening among PLHIV was of high yield and modest cost when combined with TPT. Our findings support WHO recommendations for routine TB disease screening among PLHIV.

Breast Tuberculosis in Iran: A Comprehensive Review.

ABSTRACT: Tuberculosis (TB) remains a significant global health concern and kills millions of people every year. While TB can affect any organ in the body, breast TB is relatively uncommon. This study presents a comprehensive review of literature spanning 23 years, with a focus on cases of breast TB in Iran. Among the 96 cases found, the majority (89.6%) fell within the age range of 20-60, with a striking prevalence among women (98.9%). Common symptoms included pain and palpable mass, each presenting in approximately 60.4% of cases. Notably, only a quarter of patients had a confirmed history of exposure to a known TB case. Left breast involvement was more prevalent (58.3%), with ipsilateral lymph node enlargement observed in 40.6% of cases. Given the clinical presentation of breast TB, which often leads to misdiagnosis, a significant proportion of cases (68.7%) were diagnosed through excisional biopsy. Following a standard 6-month regimen of anti-TB drugs, relapse occurred in only 4.2% of cases. This study highlights the need for heightened awareness and vigilance in diagnosing breast TB, especially in regions with a high burden. Although breast TB poses diagnostic challenges, with prompt identification and treatment, the prognosis is generally favorable, with a low incidence of relapse.

Evaluation of clinical profiles, imaging findings and antituberculosis treatment outcome in granulomatous mastitis: An Indian scenario.

BACKGROUND: The management of choice for granulomatous mastitis (GM) has yet to be determined but few studies have demonstrated that anti-tubercular treatment (ATT) could be an effective alternative therapeutic option. Hence, the objective of the current study is to determine the clinical feature, radiological imaging findings, and histopathological examination results exhibited by GM and tuberculosis (TB)-proven GM as well as to evaluate the ATT clinical outcome in GM patients. METHODS: The study was performed on 68 GM patients who were referred to the department of pulmonology by the breast clinic (from January 2018 to August 2021). Study populations were categorized into two groups GM and TB-proven GM patients and all were prescribed with standard ATT regimen and were continuously followed up. SPSS version 25 was employed for statistical assessment. RESULTS: Our study showed that 6 patients from GM and 4 patients from the TB-proven GM group got relapsed. For patients who displayed partial remission, ATT treatment was started after assessing the side effects potential. 14.6% (n = 6) and 7.4% (n = 2) patients who initially demonstrated partial remission were also completely cured. ATT treatment curable rate was determined to be 90% (n = 37) and 81.5% (n = 22) for GM and TB-proven GM patients correspondingly. Therefore, the current study demonstrated nil significant differences between groups. CONCLUSION: The current study warrants that ATT therapy could be an effective and better treatment of choice for GM patients irrespective of their clinical condition.

Diagnostic accuracy of tests for tuberculous pericarditis: A network meta-analysis.

Tuberculous pericarditis (TBP) is a relatively uncommon but potentially fatal extrapulmonary manifestation of tuberculosis. Despite its severity, there is no universally accepted gold standard diagnostic test for TBP currently. The objective of this study is to compare the diagnostic accuracy of the most commonly used tests in terms of specificity, sensitivity, negative predictive value (NPV), and positive predictive value (PPV), and provide a summary of their diagnostic accuracies. A comprehensive literature review was performed using Scopus, MEDLINE, and Cochrane central register of controlled trials, encompassing studies published from start to April 2022. Studies that compared Interferon Gamma Release Assay (IGRA), Xpert MTB/RIF, Adenosine Deaminase levels (ADA), and Smear Microscopy (SM) were included in the analysis. Bayesian random-effects model was used for statistical analysis and mean and standard deviation (SD) with 95% confidence intervals were calculated using the absolute risk (AR) and odds ratio (OR). Rank probability and heterogeneity were determined using risk difference and Cochran Q test, respectively. Sensitivity and specificity were evaluated using true negative, true positive, false positive, and false negative rates. Area under the receiver operating characteristic (AUROC) was calculated for mean and standard error. A total of seven studies comprising 16 arms and 618 patients were included in the analysis. IGRA exhibited the highest mean (SD) sensitivity of 0.934 (0.049), with a high rank probability of 87.5% for being the best diagnostic test, and the AUROC was found to be 94.8 (0.36). On the other hand, SM demonstrated the highest mean (SD) specificity of 0.999 (0.011), with a rank probability of 99.5%, but a leave-one-out analysis excluding SM studies revealed that Xpert MTB/RIF ranked highest for specificity, with a mean (SD) of 0.962 (0.064). The diagnostic tests compared in our study exhibited similar high NPV, while ADA was found to have the lowest PPV among the evaluated methods. Further research, including comparative studies, should be conducted using a standardized cutoff value for both ADA levels and IGRA to mitigate the risk of threshold effect and minimize bias and heterogeneity in data analysis.

Evaluation of a population-wide, systematic screening initiative for tuberculosis on Daru island, Western Province, Papua New Guinea.

BACKGROUND: A population-wide, systematic screening initiative for tuberculosis (TB) was implemented on Daru island in the Western Province of Papua New Guinea, where TB is known to be highly prevalent. The initiative used a mobile van equipped with a digital X-ray device, computer-aided detection (CAD) software to identify TB-related abnormalities on chest radiographs, and GeneXpert machines for follow-on diagnostic testing. We describe the results of the TB screening initiative, evaluate its population-level impact and examine risk factors associated with TB detection. METHODS: Through a retrospective review of screening data, we assessed the effectiveness of the screening by examining the enrolment coverage and the proportion of people with TB among screened subjects. A cascade analysis was performed to illustrate the flow of participants in the screening algorithm. We conducted univariate and multivariate analyses to identify factors associated with TB. Furthermore, we estimated the number of additional cases detected by the project by examining the trend of routine TB case notifications during the intervention period, compared to the historical baseline cases and trend-adjusted expected cases. RESULTS: Of the island's 18,854 residents, 8,085 (42.9%) were enrolled and 7,970 (98.6%) had chest X-ray interpreted by the CAD4TB software. A total of 1,116 (14.0%) participants were considered to have abnormal CXR. A total of 69 Xpert-positive cases were diagnosed, resulting in a detection rate of 853 per 100 000 population screened. 19.4% of people with TB had resistance to rifampicin. People who were in older age groups (aOR 6.6, 95%CI: 1.5-29.1 for the 45-59 age group), were severely underweight (aOR 2.5, 95%CI:1.0-6.1) or underweight (aOR 2.1, 95%CI: 1.1-3.8), lived in households < 5 people (aOR 3.4, 95%CI:1.8-6.6) and had a past history of TB (aOR 2.1, 95%CI: 1.2-3.6) were more likely to have TB. The number of bacteriologically confirmed TB notified during the intervention period was 79.3% and 90.8% higher than baseline notifications and forecasted notifications, respectively. CONCLUSION: The screening project demonstrated its effectiveness with the high Xpert-positive TB prevalence among the participants and by successfully yielding additional cases of bacteriologically confirmed TB including rifampicin-resistant TB. The results and lessons learnt from the project should inform future TB screening initiatives in Papua New Guinea.

Real-time evaluation of a multi-agency TB-screening event for persons experiencing homelessness in a town with a low incidence of TB in England.

Real-time evaluation (RTE) supports populations (e.g., persons experiencing homelessness (PEH) to engage in evaluation of health interventions who may otherwise be overlooked. The aim of this RTE was to explore the understanding of TB amongst PEH, identify barriers/facilitators to attending screening for PEH alongside suggestions for improving TB-screening events targeting PEH, who have high and complex health needs. This RTE composed of free-text structured one-to-one interviews performed immediately after screening at a single tuberculosis (TB) screening event. Handwritten forms were transcribed for thematic analysis, with codes ascribed to answers that were developed into core themes. All RTE participants (n=15) learned about the screening event on the day it was held. Key concerns amongst screening attendees included: stigma around drug use, not understanding the purpose of TB screening, lack of trusted individuals/services present, too many partner organizations involved, and language barriers. Facilitators to screening included a positive welcome to the event, a satisfactory explanation of screening tests, and sharing of results. A need for improved event promotion alongside communication of the purpose of TB screening amongst PEH was also identified. A lack of trust identified by some participants suggests the range of services present should be reconsidered for future screening events.

The plasma kynurenine-to-tryptophan ratio as a biomarker of tuberculosis disease in people living with HIV on antiretroviral therapy: an exploratory nested case-control study.

BACKGROUND: Non-sputum-based tests are needed to predict or diagnose tuberculosis (TB) disease in people living with HIV (PWH). The enzyme indoleamine 2, 3-dioxygenase-1 (IDO1) is expressed in tuberculoid granuloma and catabolizes tryptophan (Trp) to kynurenine (Kyn). IDO1 activity compromises innate and adaptive immune responses, promoting mycobacterial survival. The plasma Kyn-to-Trp (K/T) ratio is a potential TB diagnostic and/or predictive biomarker in PWH on long-term antiretroviral therapy (ART). METHODS: We compared plasma K/T ratios in samples from PWH, who were followed up prospectively and developed TB disease after ART initiation. Controls were matched for age and duration of ART. Kyn and Trp were measured at 3 timepoints; at TB diagnosis, 6 months before TB diagnosis and 6 months after TB diagnosis, using ultra performance liquid chromatography combined with mass spectrometry. RESULTS: The K/T ratios were higher for patients with TB disease at time of diagnosis (median, 0.086; IQR, 0.069-0.123) compared to controls (0.055; IQR 0.045-0.064; p = 0.006), but not before or after TB diagnosis. K/T ratios significantly declined after successful TB treatment, but increased upon treatment failure. The K/T ratios showed a parabolic correlation with CD4 cell counts in participants with TB (p = 0.005), but there was no correlation in controls. CONCLUSIONS: The plasma K/T ratio helped identify TB disease and may serve as an adjunctive biomarker for for monitoring TB treatment in PWH. Validation studies to ascertain these findings and evaluate the optimum cut-off for diagnosis of TB disease in PWH should be undertaken in well-designed prospective cohorts. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00411983.

The use of Kudoh method for culture of Mycobacterium tuberculosis and Mycobacterium africanum in The Gambia.

BACKGROUND: Mycobacterium tuberculosis culturing remains the gold standard for laboratory diagnosis of tuberculosis. Tuberculosis remains a great public health problem in developing countries like The Gambia, as most of the methods currently used for bacterial isolation are either time-consuming or costly. OBJECTIVE: To evaluate the Kudoh swab method in a West African setting in Gambia, with a particular focus on the method's performance when culturing Mycobacterium africanum West Africa 2 (MAF2) isolates. METHOD: 75 sputum samples were collected in the Greater Banjul Area and decontaminated in parallel with both the standard N-acetyl-L-Cysteine-NaOH (NALC-NaOH) and the Kudoh swab method in the TB diagnostics laboratory in the Medical Research Council Unit The Gambia between 30th December 2017 and 25th February 2018. These samples were subsequently cultured on standard Löwenstein-Jensen and Modified Ogawa media respectively and incubated at 37°C for mycobacterial growth. Spoligotyping was done to determine if the decontamination and culture methods compared could equally detect Mycobacterium tuberculosis, Mycobacterium africanum West Africa 1 and Mycobacterium africanum West Africa 2. RESULT: Among the 50 smear positives, 35 (70%) were culture-positive with Kudoh and 32 (64%) were culture positive with NALC-NaOH, whilst 7(28%) of the 25 smear negative samples were culture positive with both methods (Table 2). There was no significant difference in recovery between both methods (McNemar's test, p-value = 0.7003), suggesting that the overall positivity rate between the two methods is comparable. There were no differences in time-to-positivity or contamination rate between the methods. However, Kudoh yielded positive cultures that were negative on LJ and vice versa. All findings were irrespective of mycobacterial lineages. CONCLUSION: The Kudoh method has comparable sensitivity to the NALC-NaOH method for detecting Mycobacterium tuberculosis complex isolates. It is easy to perform and could be an add on option for mycobacterial culture in the field in The Gambia, since it requires less biosafety equipment.