Early-life external exposome in children 2-5 years old in Colombia.

Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9-4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = -0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making.

The escalating tuberculosis crisis in central and South American prisons.

In the past decade, tuberculosis incidence has declined in much of the world, but has risen in central and South America. It is not yet clear what is driving this reversal of progress in tuberculosis control. Since 2000, the incarcerated population in central and South America has grown by 206%, the greatest increase in the world. Over the same period, notified tuberculosis cases among the incarcerated population (hereinafter termed persons deprived of their liberty [PDL], following the Inter-American Commission on Human Rights) have risen by 269%. In both central and South America, the rise of disease among PDL more than offsets tuberculosis control gains in the general population. Tuberculosis is increasingly concentrated among PDL; currently, 11% of all notified tuberculosis cases in central and South America occur among PDL who comprise less than 1% of the population. The extraordinarily high risk of acquiring tuberculosis within prisons creates a health and human rights crisis for PDL that also undermines wider tuberculosis control efforts. Controlling tuberculosis in this region will require countries to take urgent measures to prioritise the health of PDL.

Etiology and the challenge of diagnostic testing of community-acquired pneumonia in children and adolescents.

BACKGROUND: Pneumonia is the leading cause of mortality in pediatric population. The etiology of pneumonia in this population is variable and changes according to age and disease severity and where the study is conducted. Our aim was to determine the etiology of community-acquired pneumonia (CAP) in children aged 1 month to 17 years admitted to 13 Colombian hospitals. METHODS: Prospective cohort study. Hospitalized children with radiologically confirmed CAP and ≤ 15 days of symptoms were included and followed together with a control group. Induced sputum (IS) was submitted for stains and cultures for pyogenic bacteria and Mycobacterium tuberculosis, and multiplex PCR (mPCR) for bacteria and viruses; urinary antigens for pneumococcus and Legionella pneumophila; nasopharyngeal swabs for viruses, and paired serology for atypical bacteria and viruses. Additional cultures were taken at the discretion of primary care pediatricians. RESULTS: Among 525 children with CAP, 71.6% had non-severe pneumonia; 24.8% severe and 3.6% very severe pneumonia, and no fatal cases. At least one microorganism was identified in 84% of children and 61% were of mixed etiology; 72% had at least one respiratory virus, 28% pyogenic bacteria and 21% atypical bacteria. Respiratory syncytial virus, Parainfluenza, Rhinovirus, Influenza, Mycoplasma pneumoniae, Adenovirus and Streptococcus pneumoniae were the most common etiologies of CAP. Respiratory syncytial virus was more frequent in children under 2 years and in severe pneumonia. Tuberculosis was diagnosed in 2.3% of children. IS was the most useful specimen to identify the etiology (33.6%), and blood cultures were positive in 3.6%. The concordance between all available diagnostic tests was low. A high percentage of healthy children were colonized by S. pneumoniae and Haemophilus influenzae, or were infected by Parainfluenza, Rhinovirus, Influenza and Adenovirus. CONCLUSIONS: Respiratory viruses are the most frequent etiology of CAP in children and adolescents, in particular in those under 5 years. This study shows the challenges in making an etiologic diagnosis of CAP in pediatric population because of the poor concordance between tests and the high percentage of multiple microorganisms in healthy children. IS is useful for CAP diagnosis in pediatric population.

Effect of the Xpert MTB/RIF on the detection of pulmonary tuberculosis cases and rifampicin resistance in Shanghai, China.

BACKGROUND: Xpert MTB/RIF (Xpert) is an automated molecular test recommended by World Health Organization (WHO) for diagnosis of tuberculosis (TB). This study evaluated the effect of Xpert implementation on the detection of pulmonary TB (PTB) and rifampicin-resistant TB (RR-TB) cases in Shanghai, China. METHODS: Xpert was routinely implemented in 2018 for all presumptive PTB patients. All PTB patients above 15 years-old identified within the Provincial TB Control Program during the first half of each of 2017 and 2018, were enrolled to compare the difference in proportions of bacteriological confirmation, patients with drug susceptibility test (DST) results for rifampicin (ie, DST coverage) and RR-TB detection before and after Xpert's implementation. RESULTS: A total of 6047 PTB patients were included in the analysis with 1691 tested by Xpert in 2018. Percentages of bacteriological confirmation, DST coverage and RR-TB detection in 2017 and 2018 were 50% vs. 59%, 36% vs. 49% and 2% vs. 3%, respectively (all p-values < 0.05). Among 1103 PTB patients who completed sputum smear, culture and Xpert testing in 2018, Xpert detected an additional 121 (11%) PTB patients who were negative by smear and culture, but missed 248 (23%) smear and/or culture positive patients. Besides, it accounted for an increase of 9% in DST coverage and 1% in RR-TB detection. The median time from first visit to a TB hospital to RR-TB detection was 62 days (interquartile range -IQR 48-84.2) in 2017 vs. 9 days (IQR 2-45.7) in 2018 (p-value < 0.001). In the multivariate model, using Xpert was associated with decreased time to RR-TB detection (adjusted hazard ratio = 4.62, 95% confidence interval: 3.18-6.71). CONCLUSIONS: Integrating Xpert with smear, culture and culture-based DST in a routine setting significantly increased bacteriological confirmation, DST coverage and RR-TB detection with a dramatic reduction in the time to RR-TB diagnosis in Shanghai, China. Our findings can be useful for other regions that attempt to integrate Xpert into routine PTB and RR-TB case-finding cascade. Further study should focus on the identification and elimination of operational level challenges to fully utilize the benefit of rapid diagnosis by Xpert.

High transient colonization by Pneumocystis jirovecii between mothers and newborn.

The aim of the study was to explore the frequency and dynamics of acquisition and colonization of Pneumocystis jirovecii among neonates, as well as the epidemiological and genotypic characteristics in mother-child binomial. In a prospective enrolled cohort of women in their third trimester of pregnancy, nasopharyngeal swabs (NPS) and clinical and epidemiological data were collected at four different times: 17 days, 2nd, 4th, and 6th month of life of the newborn. P. jirovecii was detected by nested-PCR for the mtLSU-rRNA gene in each NPS; the genotypes were determined amplifying four genes. Forty-three pairs and 301 NPS were included. During the third trimester, 16.3% of pregnant women were colonized. The rate of colonization in mothers at delivery was 16, 6, 16, and 5% and in their children 28, 43, 42, and 25%, respectively. Within pregnant women, 53% remained negative throughout follow-up, and among these, 91% of their children were positive in at least one of their samples. In both, mothers and children, the most frequent genotype of P. jirovecii was 1. CONCLUSION: The frequency of colonization by P. jirovecii was higher in newborns than in their respective progenitors. Colonization of both mothers and children is transitory; however, the mother of the newborn is not necessarily the source of primary infection. What is Known: • We did not find studies comparing P. jirovecii colonization between mothers and children simultaneously, yet the frequency of colonization by serologic and molecular methods in pregnant women has been reported. What is New: • According to our findings, 3/4 of the children had transient colonization during the first 6 months of life, in only half in the mothers, without proof of mother-to-child transmission or vice versa.

Comparison of serological methods with PCR-based methods for the diagnosis of community-acquired pneumonia caused by atypical bacteria.

BACKGROUND: The diagnosis of community-acquired pneumonia (CAP) caused by Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae is traditionally based on cultures and serology, which have special requirements, are time-consuming, and offer delayed results that limit their clinical usefulness of these techniques. We sought to develop a multiplex PCR (mPCR) method to diagnosis these bacterial infections in CAP patients and to compare the diagnostic yields obtained from mPCR of nasopharyngeal aspirates (NPAs), nasopharyngeal swabs (NPSs), and induced sputum (IS) with those obtained with specific PCR commercial kits, paired serology, and urinary antigen. RESULTS: A total of 225 persons were included. Of these, 10 patients showed serological evidence of L. pneumophila infection, 30 of M. pneumoniae, and 18 of C. pneumoniae; 20 individuals showed no CAP. The sensitivities were mPCR-NPS = 23.1%, mPCR-IS = 57.1%, Seeplex®-IS = 52.4%, and Speed-oligo®-NPA/NPS = 11.1%, and the specificities were mPCR-NPS = 97.1%, mPCR-IS = 77.8%, Seeplex®-IS = 92.6%, and Speed-oligo®-NPA/NPS = 96.1%. The concordance between tests was poor (kappa <0.4), except for the concordance between mPCR and the commercial kit in IS (0.67). In individuals with no evidence of CAP, positive reactions were observed in paired serology and in all PCRs. CONCLUSIONS: All PCRs had good specificity but low sensitivity in nasopharyngeal samples. The sensitivity of mPCR and Seeplex® in IS was approximately 60%; thus, better diagnostic techniques for these three bacteria are required.

Prevalence of dyslalias in 8 to 16 year-old students with anterior open bite in the municipality of Envigado, Colombia.

BACKGROUND: Anterior open bite AOB is the most common malocclusion associated with speech disorders and the literature has shown that problems of occlusion involve all oral functions. AOB not only produce aesthetic and occlusal problems for the patient and modifies the union of the lips, tongue, teeth, palate, palatal rugae and oropharynx, and thus affecting the ability to communicate well with their surroundings. The prevalence of AOB in children and adolescent in our population is unknown. Furthermore, the most frequent type of dyslalias in children with this malocclusion is also unknown. Therefore, the aim of the study was to describe the frequency and types of dyslalia in students between 8-16 years with AOB, as well as the difference in the types of dyslalia according to the magnitude of AOB. METHODS: A cross-sectional study was conducted. Clinical assessment of AOB in students from the municipality of Envigado, Colombia, was performed. Students from 8 to 16 years of age were examined during the second semester of 2011 and first semester of 2012. Phonoaudiological assessment was carried out in students in the mixed or permanent dentition. Exclusion criteria included children with history of systemic disease, altered skeletal development, neurological and psychiatric disorders, and residents in other departments. In addition, students undergoing orthodontic treatment at the time of evaluation or with history of previous orthodontic treatment, as well as those who did not cooperate with the oral cavity evaluation, were excluded. RESULTS: Six thousand one hundred sixty five children were evaluated. One hundred sixty six presented AOB (prevalence: 2.7 %; 95 % CI: 2.28-3.10). Thirty four students were excluded. 26.5 % of the sample presented mild AOB, 66.7 % moderate, and 6.8 % severe. Some type of dyslalia was found in 77.4 % of the students, being distortion (75.8 %) the most common. The most frequently altered phonemes were: / d / t / s / ch / ñ /. No significant association between different types of dyslalia and AOB severity (p-value = 0.974) was found. CONCLUSION: Prevalence of AOB in Envigado is low (2.7 %). Phonation alterations are very common in children with AOB (77.8 %), and distortion is the most frequent type of dyslalia (75.8 %). In order to diagnose and treat occlusal and phonetic problems, and to avoid possible recurrence, interdisciplinary approach is recommended.

Optimal force for maxillary protraction facemask therapy in the early treatment of class III malocclusion.

BACKGROUND: The facemask is used to treat early class III malocclusion, in combination with expansion therapy. There is a great deal of controversy in literature regarding the effectiveness of protraction facemask treatment as studies report results anywhere from considerable changes to lack of any maxillary improvement. This controversy may be due to the fact that the process of placing the orthopaedic facemask on patients has, in part, been done empirically, without the use of literature containing the clinical parameters for facemask placement for maxillary protraction. OBJECTIVE: To determine the optimal magnitude, duration, and direction that should be used in maxillary protraction facemask therapy. SEARCH METHODS: A systematic search was carried out in the following databases: Medline, Google Scholar, Embase, Cochrane, Lilacs, Scielo, with no restriction placed on the year of publication, in English and Spanish, using MeSH terms and free-text terms. SELECTION CRITERIA: Clinical trials, systematic reviews, meta-analysis, cohort studies, case-control studies, and cross-sectional studies were included, whereas literature reviews, case reports, case series, symposiums, compendiums, pilot studies, and expert opinions were excluded. DATA COLLECTION AND ANALYSIS: Data selection and extraction were blinded and performed independently, and the methodology was evaluated using various scales. RESULTS: A total of 223 articles were found. After eliminating repeated articles and those that did not meet the selection criteria, 14 remained for analysis. Regarding magnitude, there were values ranging from 180 to 800g per side; there were force vector direction values between 20 and 30 degrees below the occlusal plane or parallel to the occlusal plane; and a duration ranging from 10 to 24 hours of use per day. CONCLUSIONS: There is no scientific evidence that would allow for the definition of adequate parameters for force magnitude, direction, and duration for maxillary protraction facemask treatment in class III patients.

Agreement between cranial and facial classification through clinical observation and anthropometric measurement among Envigado school children.

BACKGROUND: To evaluate the agreement between cranial and facial classification obtained by clinical observation and anthropometric measurements among school children from the municipality of Envigado, Colombia. METHODS: This cross-sectional study was carried out among 8-15-year-old children. Initially, an indirect clinical observation was made to determine the skull pattern (dolichocephalic, mesocephalic or brachycephalic), based on visual equivalence of right eurion- left eurion and glabella-opisthocranion anthropometric points, as well as the facial type (leptoprosopic, mesoprosopic and euryprosopic), according to the left and right zygomatic, nasion and gnation points. Following, a direct measurement was conducted with an anthropometer using the same landmarks for cranial width and length, as well as for facial width and height. Subsequently, both the facial index [euryprosopic (≤80.9%), mesoprosopic (between 81% - 93%) and leptoprosopic (≥93.1%)] and the cranial index [dolichocephalic (index ≤ 75.9%), mesocephalic (between 76% - 81%), and brachycephalic (≥81.1%)] were determined. Concordance between the indices obtained was calculated by direct and indirect measurement using the Kappa statistic. RESULTS: A total of 313 students were enrolled; 172 (55%) were female and 141 (45%) male. The agreement between the direct and indirect facial index measurements was 0.189 (95% CI 0.117-0261), and the cranial index was 0.388 (95% CI 0.304-0.473), indicating poor concordance. CONCLUSIONS: No agreement was observed between direct measurements conducted with an anthropometer and indirect measurements via visual evaluation. Therefore, the indirect visual classification method is not appropriate to calculate the cranial and facial indices.

Inflammatory Patterns Associated with Legionella in HIV and Pneumonia Coinfections.

Legionella infections have a propensity for occurring in HIV-infected individuals, with immunosuppressed individuals tending to present with more severe disease. However, understanding regarding the Legionella host response in immune compromised individuals is lacking. This study investigated the inflammatory profiles associated with Legionella infection in patients hospitalized with HIV and pneumonia in Medellín, Colombia from February 2007 to April 2014, and correlated these profiles with clinical outcomes. Sample aliquots from the Colombian cohort were shipped to Canada where Legionella infections and systemic cytokine profiles were determined using real-time PCR and bead-based technology, respectively. To determine the effect of Legionella coinfection on clinical outcome, a patient database was consulted, comparing laboratory results and outcomes between Legionella-positive and -negative individuals. Principal component analysis revealed higher plasma concentrations of eotaxin, IP-10 and MCP-1 (p = 0.0046) during Legionella infection. Individuals with this immune profile also had higher rates of intensive care unit admissions (adjusted relative risk 1.047 [95% confidence interval 1.027-1.066]). Results demonstrate that systemic markers of monocyte/macrophage activation and differentiation (eotaxin, MCP-1, and IP-10) are associated with Legionella infection and worse patient outcomes. Further investigations are warranted to determine how this cytokine profile may play a role in Legionella pneumonia pathogenesis or immunity.

Knowledge, attitudes and practices about air pollution and its health effects in 6th to 11th-grade students in Colombia: a cross-sectional study.

Introduction: Globally, air pollution is the leading environmental cause of disease and premature death. Raising awareness through environmental education and adequate communication on air quality could reduce the adverse effects. We aimed to assess the knowledge, attitudes, and practices (KAP) regarding air pollution and health and determine the factors associated with these KAP in children and adolescents. Methods: In 2019-2020, a cross-sectional study was conducted on 6th-11th grade high school students in five municipalities in Colombia. Variables collected included: age, sex, private or public school, any medical history, emergency room visits due to respiratory symptoms in the last year, and whether students played sports. The main exposure was the School Environmental Project. The outcomes were the KAP scale [0% (the lowest score) to 100% (the highest score)]. The factors associated with KAP levels were evaluated with independent mixed regressions due to the multilevel structure of the study (level 1: student; level 2: school), and the exponential coefficients (95% confidence interval-CI) were reported. Results: Among 1,676 students included, 53.8% were females. The median knowledge score about air pollution and its health effects was 33.8% (IQR: 24.0-44.9), 38.6% knew the air quality index, 30.9% knew the air quality alerts that occurred twice a year in these municipalities and 5.3% had high self-perceived knowledge. Positive attitudes, pro-environmental practices, being female, grade level, attending a private school, having respiratory diseases, and the school environmental project importance were associated with higher knowledge scores. The median attitudes score was 78.6% (IQR: 71.4-92.9). Pro-environmental attitudes were associated with knowledge-increasing, being female, attending a private school, and the school environmental project. The median pro-environmental practices score was 28.6% (IQR: 28.6-42.9). During air quality alerts, 11.6% had worn masks, 19% had reduced the opening time of windows and 15.9% avoided leaving home. Pro-environmental practices were associated with knowledge-increasing and attitudes-increasing, and lower practices with higher grade levels, visiting a doctor in the last year, and practicing sports. Discussion: Children and adolescents have low knowledge scores and inadequate pro-environmental practices scores regarding air pollution. However, they demonstrate positive attitudes towards alternative solutions and express important concerns about the planet's future.

Sex differences in houselessness, injection drug use, and mental health conditions among people newly diagnosed with HIV in Manitoba, Canada from 2018 to 2021: a retrospective cohort study.

Background: Manitoba saw the highest number of new HIV diagnoses in the province's history in 2021 and is the only Canadian province not meeting any of the previous UNAIDS 90-90-90 targets. Our goal was to describe sex differences and syndemic conditions within an incident HIV cohort in Manitoba, and the HIV treatment initiation and undetectable viral load outcomes. Methods: This was a retrospective cohort study of all people 18 years and older newly diagnosed with HIV in Manitoba, Canada between January 1st, 2018 and December 31st, 2021. Data was collected as follows: before HIV diagnosis: chlamydia, gonorrhoea, syphilis, and/or hepatitis C antibodies. At the time of HIV diagnosis: age, sex, gender, race/ethnicity, sexual orientation. During follow-up: CD4 counts, viral load, HIV treatment, hospitalizations, and number of visits to HIV care. Main exposures evaluated: methamphetamine use, injection drug use, houselessness, and mental health conditions. Outcomes: started antiretroviral treatment and achieved an undetectable viral load. A descriptive statistical analysis was used. Findings: There were 404 new HIV diagnoses in Manitoba from 2018 to 2021; 44.8% were female, 55.2% male; 76.% self-identified as Indigenous, 13.4% white/European, 4.7% African/black; 86.6% cis-gender; 60.9% heterosexual, 13.4% gay, bisexual and men who have sex with men, and 1.7% lesbian. Injection drug use was reported by 71.8% and 43.5% of females and males respectively. Methamphetamine was the most frequently injected drug (62.4%). Amongst females, 81.8% experienced at least one of the following: houselessness (43.1%), mental health comorbidities (46.4%), and injection drug use (71.8%). Only 64.9% of all individuals had an undetectable viral load (61.1% females and 67.9% males), 56.5% among people experiencing houselessness, 59% among young people (≤29 years), and 60.1% among people who inject drugs. Interpretation: People newly diagnosed with HIV in Manitoba are disproportionately experiencing houselessness, mental illness, and injection drug use (mostly methamphetamine). This pattern is more pronounced for female individuals. These findings highlight the need for syndemic and gender-specific approaches, simultaneously addressing social and health conditions, to treat HIV. Funding: This work was supported by the Canadian Institutes of Health Research, The Manitoba Medical Service Foundation, The James Farley Memorial Fund and the Canada Research Chairs Program.

Does the Recovery of Respiratory Viruses Impact Pulmonary Function at Baseline and 1-, 6-, and 12-Month Follow-Up in People Living with HIV and Pneumonia?

The frequency of respiratory viruses in people living with HIV (PLHIV) and their impact on lung function remain unclear. We aimed to determine the frequency of respiratory viruses in bronchoalveolar lavage and induced sputum samples in PLHIV and correlate their presence with lung function. A prospective cohort of adults hospitalized in Medellín between September 2016 and December 2018 included three groups: group 1 = people diagnosed with HIV and a diagnosis of community-acquired pneumonia (CAP), group 2 = HIV, and group 3 = CAP. People were followed up with at months 1, 6, and 12. Clinical, microbiological, and spirometric data were collected. Respiratory viruses were detected by multiplex RT-PCR. Sixty-five patients were included. At least 1 respiratory virus was identified in 51.9%, 45.1%, and 57.1% of groups 1, 2 and 3, respectively. Among these, 89% of respiratory viruses were detected with another pathogen, mainly Mycobacterium tuberculosis (40.7%) and Pneumocystis jirovecii (22.2%). The most frequent respiratory virus was rhinovirus (24/65, 37%). On admission, 30.4% of group 1, 16.6% of group 2, and 50% of group 3 had airflow limitation, with alteration in forced expiratory volume at first second in both groups with pneumonia compared to HIV. Respiratory viruses are frequent in people diagnosed with HIV, generally coexisting with other pathogens. Pulmonary function on admission was affected in patients with pneumonia, improving significantly in the 1st, 6th, and 12th months after CAP onset.

Markers of Inflammation, Tissue Damage, and Fibrosis in Individuals Diagnosed with Human Immunodeficiency Virus and Pneumonia: A Cohort Study.

Previous studies have noted that persons living with human immunodeficiency virus (HIV) experience persistent lung dysfunction after an episode of community-acquired pneumonia (CAP), although the underlying mechanisms remain unclear. We hypothesized that inflammation during pneumonia triggers increased tissue damage and accelerated pulmonary fibrosis, resulting in a gradual loss of lung function. We carried out a prospective cohort study of people diagnosed with CAP and/or HIV between 2016 and 2018 in three clinical institutions in Medellín, Colombia. Clinical data, blood samples, and pulmonary function tests (PFTs) were collected at baseline. Forty-one patients were included, divided into two groups: HIV and CAP (n = 17) and HIV alone (n = 24). We compared the concentrations of 17 molecules and PFT values between the groups. Patients with HIV and pneumonia presented elevated levels of cytokines and chemokines (IL-6, IL-8, IL-18, IL-1RA, IL-10, IP-10, MCP-1, and MIP-1ß) compared to those with only HIV. A marked pulmonary dysfunction was evidenced by significant reductions in FEF25, FEF25-75, and FEV1. The correlation between these immune mediators and lung function parameters supports the connection between pneumonia-associated inflammation and end organ lung dysfunction. A low CD4 cell count (<200 cells/µL) predicted inflammation and lung dysfunction. These results underscore the need for targeted clinical approaches to mitigate the adverse impacts of CAP on lung function in this population.

Tuberculosis in Prisons: Importance of Considering the Clustering in the Analysis of Cross-Sectional Studies.

The level of clustering and the adjustment by cluster-robust standard errors have yet to be widely considered and reported in cross-sectional studies of tuberculosis (TB) in prisons. In two cross-sectional studies of people deprived of liberty (PDL) in Medellin, we evaluated the impact of adjustment versus failure to adjust by clustering on prevalence ratio (PR) and 95% confidence interval (CI). We used log-binomial regression, Poisson regression, generalized estimating equations (GEE), and mixed-effects regression models. We used cluster-robust standard errors and bias-corrected standard errors. The odds ratio (OR) was 20% higher than the PR when the TB prevalence was >10% in at least one of the exposure factors. When there are three levels of clusters (city, prison, and courtyard), the cluster that had the strongest effect was the courtyard, and the 95% CI estimated with GEE and mixed-effect models were narrower than those estimated with Poisson and binomial models. Exposure factors lost their significance when we used bias-corrected standard errors due to the smaller number of clusters. Tuberculosis transmission dynamics in prisons dictate a strong cluster effect that needs to be considered and adjusted for. The omission of cluster structure and bias-corrected by the small number of clusters can lead to wrong inferences.

Cytokine/chemokine profiles in people with recent infection by Mycobacterium tuberculosis.

Introduction: The risk of progression to tuberculosis disease is highest within the first year after M. tuberculosis infection (TBI). We hypothesize that people with newly acquired TBI have a unique cytokine/chemokine profile that could be used as a potential biomarker. Methods: We evaluated socio-demographic variables and 18 cytokines/chemokines in plasma samples from a cohort of people deprived of liberty (PDL) in two Colombian prisons: 47 people diagnosed with pulmonary TB, 24 with new TBI, and 47 non-infected individuals. We performed a multinomial regression to identify the immune parameters that differentiate the groups. Results: The concentration of immune parameters changed over time and was affected by the time of incarceration. The concentration of sCD14, IL-18 and IP-10 differed between individuals with new TBI and short and long times of incarceration. Among people with short incarceration, high concentrations of MIP-3α were associated with a higher risk of a new TBI, and higher concentrations of Eotaxin were associated with a lower risk of a new TBI. Higher concentrations of sCD14 and TNF-α were associated with a higher risk of TB disease, and higher concentrations of IL-18 and MCP-1 were associated with a lower risk of TB disease. Conclusions: There were cytokines/chemokines associated with new TBI and TB disease. However, the concentration of immune mediators varies by the time of incarceration among people with new TBI. Further studies should evaluate the changes of these and other cytokines/chemokines over time to understand the immune mechanisms across the spectrum of TB.

Social and structural barriers and facilitators to HIV healthcare and harm reduction services for people experiencing syndemics in Manitoba: study protocol.

INTRODUCTION: In Manitoba, Canada, there has been an increase in the number of people newly diagnosed with HIV and those not returning for regular HIV care. The COVID-19 pandemic resulted in increased sex and gender disparities in disease risk and mortalities, decreased harm reduction services and reduced access to healthcare. These health crises intersect with increased drug use and drug poisoning deaths, houselessness and other structural and social factors most acutely among historically underserved groups. We aim to explore the social and structural barriers and facilitators to HIV care and harm reduction services experienced by people living with HIV (PLHIV) in Manitoba. METHODS AND ANALYSIS: Our study draws on participatory action research design. Guiding the methodological design are the lived experiences of PLHIV. In-depth semi-structured face-to-face interviews and quantitative questionnaires will be conducted with two groups: (1) persons aged ≥18 years living or newly diagnosed with HIV and (2) service providers who work with PLHIV. Data collection will include sex, gender, sociodemographic information, income and housing, experiences with the criminal justice system, sexual practices, substance use practices and harm reduction access, experiences with violence and support, HIV care journey (since diagnosis until present), childhood trauma and a decision-making questionnaire. Data will be analysed intersectionally, employing grounded theory for thematic analysis, sex-based and gender-based analysis and social determinants of health and syndemic framework to understand the experiences of PLHIV in Manitoba. ETHICS AND DISSEMINATION: We received approval from the University of Manitoba Health Ethics Research Board (HS25572; H2022:218), First Nations Health and Social Secretariat of Manitoba, Nine Circles Community Health Centre, Shared Health Manitoba (SH2022:194) and 7th Street Health Access Centre. Findings will be disseminated using community-focused knowledge translation strategies identified by participants, peers, community members and organisations, and reported in conferences, peer-reviewed journals and a website (www.alltogether4ideas.org).

Characterization of the external exposome and its contribution to the clinical respiratory and early biological effects in children: The PROMESA cohort study protocol.

BACKGROUND: Air pollution contains a mixture of different pollutants from multiple sources. However, the interaction of these pollutants with other environmental exposures, as well as their harmful effects on children under five in tropical countries, is not well known. OBJECTIVE: This study aims to characterize the external exposome (ambient and indoor exposures) and its contribution to clinical respiratory and early biological effects in children. MATERIALS AND METHODS: A cohort study will be conducted on children under five (n = 500) with a one-year follow-up. Enrolled children will be followed monthly (phone call) and at months 6 and 12 (in person) post-enrolment with upper and lower Acute Respiratory Infections (ARI) examinations, asthma development, asthma control, and genotoxic damage. The asthma diagnosis will be pediatric pulmonologist-based and a standardized protocol will be used. Exposure, effect, and susceptibility biomarkers will be measured on buccal cells samples. For environmental exposures PM2.5 will be sampled, and questionnaires, geographic information, dispersion models and Land Use Regression models for PM2.5 and NO2 will be used. Different statistical methods that include Bayesian and machine learning techniques will be used for the ambient and indoor exposures-and outcomes. This study was approved by the ethics committee at Universidad Pontificia Bolivariana. EXPECTED STUDY OUTCOMES/FINDINGS: To estimate i) The toxic effect of particulate matter transcending the approach based on pollutant concentration levels; ii) The risk of developing an upper and lower ARI, based on different exposure windows; iii) A baseline of early biological damage in children under five, and describe its progression after a one-year follow-up; and iv) How physical and chemical PM2.5 characteristics influence toxicity and children's health.

Increased susceptibility to pneumonia due to tumour necrosis factor inhibition and prospective immune system rescue via immunotherapy.

Immunomodulators such as tumour necrosis factor (TNF) inhibitors are used to treat autoimmune conditions by reducing the magnitude of the innate immune response. Dampened innate responses pose an increased risk of new infections by opportunistic pathogens and reactivation of pre-existing latent infections. The alteration in immune response predisposes to increased severity of infections. TNF inhibitors are used to treat autoimmune conditions such as rheumatoid arthritis, juvenile arthritis, psoriatic arthritis, transplant recipients, and inflammatory bowel disease. The efficacies of immunomodulators are shown to be varied, even among those that target the same pathways. Monoclonal antibody-based TNF inhibitors have been shown to induce stronger immunosuppression when compared to their receptor-based counterparts. The variability in activity also translates to differences in risk for infection, moreover, parallel, or sequential use of immunosuppressive drugs and corticosteroids makes it difficult to accurately attribute the risk of infection to a single immunomodulatory drug. Among recipients of TNF inhibitors, Mycobacterium tuberculosis has been shown to be responsible for 12.5-59% of all infections; Pneumocystis jirovecii has been responsible for 20% of all non-viral infections; and Legionella pneumophila infections occur at 13-21 times the rate of the general population. This review will outline the mechanism of immune modulation caused by TNF inhibitors and how they predispose to infection with a focus on Mycobacterium tuberculosis, Legionella pneumophila, and Pneumocystis jirovecii. This review will then explore and evaluate how other immunomodulators and host-directed treatments influence these infections and the severity of the resulting infection to mitigate or treat TNF inhibitor-associated infections alongside antibiotics.

Effect of flight connectivity on the introduction and evolution of the COVID-19 outbreak in Canadian provinces and territories.

BACKGROUND: The COVID-19 pandemic has challenged health services and governments in Canada and around the world. Our research aims to evaluate the effect of domestic and international air travel patterns on the COVID-19 pandemic in Canadian provinces and territories. METHODS: Air travel data were obtained through licensed access to the 'BlueDot Intelligence Platform', BlueDot Inc. Daily provincial and territorial COVID-19 cases for Canada and global figures, including mortality, cases recovered and population data were downloaded from public datasets. The effects of domestic and international air travel and passenger volume on the number of local and non-local infected people in each Canadian province and territory were evaluated with a semi-Markov model. Provinces and territories are grouped into large (>100 000 confirmed COVID-19 cases and >1 000 000 inhabitants) and small jurisdictions (≤100 000 confirmed COVID-19 cases and ≤1 000 000 inhabitants). RESULTS: Our results show a clear decline in passenger volumes from March 2020 due to public health policies, interventions and other measures taken to limit or control the spread of COVID-19. As the measures were eased, some provinces and territories saw small increases in passenger volumes, although travel remained below pre-pandemic levels. During the early phase of disease introduction, the burden of illness is determined by the connectivity of jurisdictions. In provinces with a larger population and greater connectivity, the burden of illness is driven by case importation, although local transmission rapidly replaces imported cases as the most important driver of increasing new infections. In smaller jurisdictions, a steep increase in cases is seen after importation, leading to outbreaks within the community. CONCLUSIONS: Historical travel volumes, combined with data on an emerging infection, are useful to understand the behaviour of an infectious agent in regions of Canada with different connectivity and population size. Historical travel information is important for public health planning and pandemic resource allocation.