New diagnostics for the spectrum of asymptomatic TB: from infection to subclinical disease.

TB remains a leading cause of morbidity and mortality worldwide. However, most infected immunocompetent individuals are asymptomatic and only 5-10% of these will eventually develop active TB during their lifetime (typically within 2 years after exposure). Therefore, rapid diagnosis and efficient management of asymptomatic infected individuals who are at the highest risk of progression and transmission remain major clinical and public health challenges. In recent years, there has been important scientific progress in our understanding of the spectrum of asymptomatic Mycobacterium tuberculosis (Mtb) infections that not only includes the dynamic state of latent TB infection (LTBI), but also the preclinical state of incipient and subclinical TB. The latter is possibly as prevalent as symptomatically active TB and potentially contributes to global Mtb transmission in various settings. We summarize the latest developments and current challenges of the existing testing tools for LTBI and describe promising biomarkers and diagnostics for the spectrum of asymptomatic TB. Following the negative results of a recent clinical trial for a biomarker-guided preventive therapy approach, we also suggest some treatment options for incipient TB.

Clinical standards for the assessment, management and rehabilitation of post-TB lung disease.

BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.

Outcome of treatment of MDR-TB or drug-resistant patients treated with bedaquiline and delamanid: Results from a large global cohort.

The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.

Rifampin pharmacokinetics in tuberculosis-diabetes mellitus patients: a pilot study from Baja California, Mexico.

BACKGROUND: Worldwide, there has been an increase in type 2 diabetes mellitus (DM2) as a comorbidity of tuberculosis (TB), which is characterized by alterations in the pharmacokinetics of drugs used for TB treatment.OBJECTIVE: To characterize the pharmacokinetics of rifampin in patients with TB and TB-DM2.METHODS: Blood samples were collected in two hospitals in Baja California, Mexico from March through December 2017. Sampling was not random and included 14 patients with TB and 16 with TB-DM2. High-performance liquid chromatographic (HPLC) was carried out to determine the concentration of rifampin in human serum.RESULTS: On average, the highest concentration of rifampin for both groups was registered at 2.5 h after ingestion (3.5 ± 2.64 µg/ml). The maximum difference in concentration (Cmax) of rifampin between TB and TB-DM2 group was not significant (P > 0.05). Importantly however, the analysis showed suboptimal levels of Cmax in a high proportion of both groups of patients studied.CONCLUSION: The study suggests that under the currently recommended rifampin dose, suboptimal Cmax levels are reached in a high proportion of patients, regardless of whether they have diabetes or not. It may therefore be necessary to use higher doses of rifampin and perform routine monitoring of serum levels. However, further work is needed to confirm these findings.

Chronic airway obstruction after successful treatment of tuberculosis and its impact on quality of life.

SETTING: Tuberculosis (TB) clinic in Tijuana, México. BACKGROUND: Chronic airway obstruction (CAO) can be a sequella of pulmonary tuberculosis (PTB), independently of smoking history. OBJECTIVE: To determine the prevalence of CAO in subjects recently recorded as cured after treatment of PTB, and its impact on quality of life. DESIGN: Cross-sectional study. RESULTS: Overall, 34.3% of patients with a history of PTB had non-reversible CAO, defined as FEV1 <70% post-bronchodilator. Subjects with CAO had significantly more radiographic fibrocavitary sequellae on chest X-rays, more extensive changes (1.8 ± 0.8 affected quadrants vs. 1.3 ± 0.6, P = 0.04), more residual lung cavities (1.4 ± 0.8 vs. 0.5 ± 0.7, P = 0.002), and greater mediastinal retraction (42.4% vs. 16.7%, P = 0.026). The mean COPD Assessment Test score for subjects with CAO was 15.1 ± 10.4. The prevalence of irreversible CAO using the lower limit of normal criteria was higher (40%) than that calculated with fixed ratio criteria (34.3%). CONCLUSION: Functional abnormalities are frequently already present at the end of treatment for PTB; patients with CAO are often symptomatic and experience a significant impact on quality of life.

Latent tuberculous infection prevalence among paediatric contacts of drug-resistant and drug-susceptible cases.

SETTING: Tuberculosis (TB) clinic in Tijuana, México. BACKGROUND: Tuberculin conversion rates in contacts of drug-resistant cases have been reported to be lower than among contacts of drug-susceptible cases. OBJECTIVE: To determine if the prevalence of latent tuberculous infection (LTBI) among paediatric contacts of drug-resistant cases is lower than that of contacts of drug-susceptible cases. DESIGN: In a cross-sectional study, LTBI among paediatric contacts of culture-proven TB cases was evaluated using the tuberculin skin test and interferon-gamma release assay. Rates among contacts of drug-susceptible and drug-resistant cases were compared. RESULTS: The TST was positive in 83.1% of the drug-susceptible group vs. 76.0% for the drug-resistant group (P = 0.25). Using the QuantiFERON Gold In-Tube (QFT-GIT) assay, drug-resistant cases had a higher rate of positivity than the drug-susceptible group, although this difference did not reach statistical significance (42.3% positivity among drug-susceptible cases vs. 57.7% among drug-resistant cases; P = 0.48). CONCLUSIONS: The proportion of LTBI is similar among paediatric contacts, regardless of whether the index case is drug-resistant or -susceptible.

Dose-response association between salivary cotinine levels and Mycobacterium tuberculosis infection.

SETTING: Tijuana, Mexico. OBJECTIVE: To describe the association between salivary cotinine levels and interferon-gamma (IFN-γ) release assay results. DESIGN: We conducted a cross-sectional study among injection drug users. Salivary cotinine levels were measured using NicAlert, a semi-quantitative dipstick assay. QuantiFERON©-TB Gold In-Tube (QFT-GIT) was used to determine Mycobacterium tuberculosis infection. RESULTS: Among 234 participants, the prevalence of QFT-GIT positivity for NicAlert cotinine categories 0 (non-smoking), 1 (second-hand smoke exposure or low-level smoking) and 26 (regular smoking) were respectively 42.1%, 46.4% and 65.2% (Ptrend 0.012). We found increasing trends in QFT-GIT positivity (Ptrend 0.003) and IFN-γ concentrations (Spearman's r 0.200, P 0.002) across cotinine levels 0 to 6. In multivariable log-binomial regression models adjusted for education, cotinine levels were not associated with QFT-GIT positivity when included as smoking categories (1 and 26 vs. 0), but were independently associated with QFT-GIT positivity when included as an ordinal variable (prevalence ratio 1.09 per 1 cotinine level, 95%CI 1.021.16). CONCLUSION: Our findings suggest that a dose-response relationship exists between tobacco smoke exposure and M. tuberculosis infection. Longitudinal studies that use biochemical measures for smoking status are needed to confirm our findings.

Social, economic, and psychological impacts of MDR-TB treatment in Tijuana, Mexico: a patient's perspective.

SETTING: The State of Baja California, Mexico, had the highest prevalence of multidrug-resistant tuberculosis (MDR-TB) in Mexico in 2009. OBJECTIVE: To understand the socio-economic burden of MDR-TB disease and its treatment on patients in Tijuana and Mexicali, Mexico. DESIGN: From July to November 2009, qualitative interviews were conducted with 12 patients enrolled in a US-Mexico binational MDR-TB treatment program, Puentes de Esperanza (Bridges of Hope), which was designed to support MDR-TB patients. In-depth interviews were coded to identify major themes in patient experiences of MDR-TB diagnosis and care. RESULTS: While some patients were able to maintain their pre-MDR-TB lives to a limited extent, most patients reported losing their sense of identity due to their inability to work, social isolation, and stigmatization from family and friends. The majority of participants expressed appreciation for Puentes' role in 'saving their lives'. CONCLUSION: Being diagnosed with MDR-TB and undergoing treatment imposes significant psychological, social and economic stress on patients. Strong social support elements within Puentes helped alleviate these burdens. Improvements to the program might include peer-support groups for patients undergoing treatment and transitioning back into the community after treatment.

Treatment of multidrug-resistant tuberculosis in a high-prevalence region through a binational consortium.

We describe the outcome of treatment of multidrug-resistant tuberculosis (MDR-TB) in Baja California, Mexico, by a United States-Mexico consortium. From June 2006 to December 2010, 42 patients started treatment. Strains were resistant to 4.15 ± 1.3 drugs; all patients achieved culture conversion on treatment after an average of 3.4 ± 1.6 months. A total of 19 patients (47.5%) were discharged as cured, 3 died (7.5%) and 1 defaulted (2.5%). MDR-TB cases can be cured under a well-organized out-patient program; in this consortium, the US partner introduced program elements that were gradually integrated into the Mexican state TB program.

Chronic obstructive pulmonary disease case finding in Mexico in an at-risk population.

OBJECTIVE: To apply a case-finding strategy in Mexico to identify chronic airway obstruction among individuals with risk factors and/or symptoms compatible with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: Individuals aged ≥ 40 years with known risk factors and/or symptoms compatible with COPD were referred for an interview and spirometry. RESULTS: Of 2293 subjects included, 472 (20.6%) had a post-bronchodilator forced expiratory volume in one second/forced vital capacity ratio of <70% (for Global Initiative for Chronic Obstructive Lung Disease [GOLD] Stages II-IV, prevalence was 17.1%). Those with airflow obstruction had smoked more cigarettes for more years than subjects without (19 vs. 13 cigarettes/day, P < 0.001, and 32 vs. 23 years, P < 0.001); they also had a more frequent history of exposure to biomass smoke (23.3% vs. 18.3%, P = 0.002). Females were exposed to biomass smoke for more years (24 vs. 19 years; P < 0.0001) and more hours per day than males (6.2 vs. 5.1; P < 0.001). In multiple logistic regression analysis, increasing age, male sex, ever smoking, pack-years of smoking and years of exposure to biomass smoke were significantly associated with COPD prevalence. CONCLUSIONS: Airflow obstruction was identified in one in five of Mexican individuals with risk factors and/or COPD symptoms. Exposure to biomass smoke was significantly associated with the presence of airflow obstruction.

Targeted screening and treatment for latent tuberculosis infection using QuantiFERON-TB Gold is cost-effective in Mexico.

OBJECTIVE: To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. DESIGN: We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. RESULTS: Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. CONCLUSIONS: In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective.

High prevalence of latent tuberculosis infection among injection drug users in Tijuana, Mexico.

BACKGROUND: We studied prevalence and correlates of latent tuberculosis infection (LTBI) among injection drug users (IDUs) in Tijuana, Mexico, where tuberculosis (TB) is endemic. METHODS: IDUs aged > or =18 years were recruited via respondent-driven sampling (RDS) and underwent standardized interviews, human immunodeficiency virus (HIV) antibody testing and LTBI screening using Quanti-FERON((R))-TB Gold In-Tube, a whole-blood interferon-gamma release assay (IGRA). LTBI prevalence was estimated and correlates were identified using RDS-weighted logistic regression. RESULTS: Of 1020 IDUs, 681 (67%) tested IGRA-positive and 44 (4%) tested HIV-positive. Mean age was 37 years, 88% were male and 98% were Mexican-born. IGRA positivity was associated with recruitment nearest the US border (aOR 1.64, 95%CI 1.09-2.48), increasing years of injection (aOR 1.20/5 years, 95%CI 1.07-1.34), and years lived in Tijuana (aOR 1.10/5 years, 95%CI 1.03-1.18). Speaking some English (aOR 0.38, 95%CI 0.25-0.57) and injecting most often at home in the past 6 months (aOR 0.68, 95%CI 0.45-0.99) were inversely associated with IGRA positivity. DISCUSSION: Increased LTBI prevalence among IDUs in Tijuana appears to be associated with greater drug involvement. Given the high risk for HIV infection among Tijuana's IDUs, interventions are urgently needed to prevent HIV infection and treat LTBI among IDUs before these epidemics collide.

Results of directly observed treatment for tuberculosis in Ensenada, Mexico: not all DOTS programs are created equally.

SETTING: Tuberculosis (TB) program in Ensenada, Mexico. OBJECTIVE: To evaluate the impact of the DOTS strategy on adherence and cure rates in everyday practice. DESIGN: Retrospective analysis of 629 patients diagnosed with TB. MEASUREMENTS AND RESULTS: A total of 70% of the patients under directly observed treatment (DOT) were cured vs. 72.8% of those under self-administered treatment (SAT, P = 0.57). There was no difference on the length of therapy according to treatment regimen (4.82 +/- 2.41 for DOT vs. 4.93 +/- 2.16 for SAT, P = 0.61); 16.8% of patients under DOT abandoned treatment vs. 14.1% in the SAT group (P = 0.40). Logistic regression analysis confirmed the previous findings, with length of treatment under 6 months being the strongest predictive variable for treatment failure (OR 18.8, P < 0.00). The type of regimen (DOT vs. SAT) was not predictive of treatment failure (OR for failure for SAT regimen 0.65, P = 0.14). CONCLUSIONS: Cure and completion of treatment rates in our population under study did not differ significantly when comparing DOT vs. SAT. Those in charge of the DOTS programs in a given country need to assess which are the most important ingredients for success in their particular program.

[Prevalence of tuberculosis infection in students in the city of Tijuana, Mexico]. / Prevalencia de infección tuberculosa en escolares de la ciudad de Tijuana, México.

OBJECTIVE: To determine the prevalence of tuberculosis infection in school children from Tijuana, Mexico. MATERIAL AND METHODS: A study sample was randomly chosen from the municipal school registry and 1,131 elementary and high school children were included. All received one doses of PPD 5TU (Mantoux). Subjects with induration > or = 10 mm were considered positive reactors. RESULTS: The overall prevalence of positive reactors was 57%. The proportion of positive reactors was significantly higher among BCG-immunized subjects than in non-immunized individuals (59.7 vs 45.6%; p < 0.001). Correlation was not significant between age of immunization with BCG and diameter of induration. CONCLUSIONS: The prevalence of tuberculosis infection in Tijuana is extremely high; this fact has important implications in the control of tuberculosis in this region.

[Children who work on the streets of Tijuana. An epidemiological profile and the prevalence of experimentation with tobacco]. / Los niños que trabajan en las calles de Tijuana. Perfil epidemiológico y prevalencia de experimentación con tabaco.

OBJECTIVE: To develop an epidemiological profile of children that work in the streets of Tijuana, Mexico, and to determine the prevalence of cigarette smoking in this group, as well as the prevalence of those factors associated with tobacco experimentation. STUDY TYPE: cross-sectional. MATERIAL AND METHODS: Children aged 8 through 15, who work in the streets of Tijuana were included. Demographic, socioeconomic, and smoking related variables were analyzed. RESULTS: The study included 110 children, with a mean age of 11.43 years. Of these 91.7% live with one or both of their parents; 60% attend school and an additional 30% did so in the past. Only 6.4% of these children are the principal economic support of the household, and 51.8% reported an average daily income of $US 10 or less. Only 9.1% reported experimentation with tobacco, and 31% of them tobacco prompting (in the form of lighting up a cigarette) by an adult of the family; this is significantly more frequent on behalf of the father than of the mother (21.8% vs 4.5% p < 0.001). CONCLUSIONS: Most of the children under 15 years of age who work in the streets of Tijuana live with their parents and maintain close relationships with their family. Most of them attend school and work in the streets only to complement the family income. Their tobacco experimentation is not greater than that of other children of the same age group.

[Observed vs expected mortality in the emergency service of a general hospital. Evaluation by the APACHE II and multiple organ failure classification systems]. / La mortalidad observada vs la mortalidad esperada en el servicio de urgencias de un hospital general. Evaluación por medio de los sistemas de APACHE II y falla orgánica múltiple.

UNLABELLED: Problem that originated the investigation: It was not known if the observed mortality in the Emergency room of the Tijuana General Hospital was lower, equal or higher, than the expected mortality. OBJECTIVES: 1) Evaluate in a prospective fashion the mortality rate in that hospital service, and then compare that rate with an expected mortality rate proposed in the literature (Role). 2) Determine the prognostic value in our hospital of the Multiple Organ Failure classification system (MOF). The Multiple Organ Failure classification system showed in our study an excellent predicting capacity for mortality.

Parental influences to smoke in Latino youth.

BACKGROUND: Latino youth have been found to have a higher prevalence of tobacco use than do other ethnic groups, possibly due to cultural factors and parental influences. METHODS: Seventh-grade students (N = 589) were surveyed in San Diego, California, and Tijuana, Mexico, to assess parental influences to smoke. These parental influence variables were studied with logistic regression, adjusting for age, sex, and number of parents who smoke. RESULTS: Among those whose parents smoke, Mexican students were asked to strike a match to light their parents' cigarettes significantly more often (57%) than Mexican-American students (37%) and U.S. Others (37%) (P < 0.05). Seventeen percent of the Mexican students reported having lit a cigarette in their own mouth for their parents, compared to 18% of Mexican-Americans and only 3% of U.S. Others (P < 0.01). Mexicans reported buying cigarettes for their parents more often (62%), compared with 36% for Mexican-Americans and 30% for U.S. Others (P < 0.01). Child smoking was only associated with friend offers of tobacco and parental prompts to light cigarettes in their mouths. CONCLUSION: Latino parents are inadvertently prompting their children to smoke. Smoking prevention programs targeting Latino youth may need to include a parental tobacco education component.

Parental prompting of smoking among adolescents in Tijuana, Mexico.

Latino adolescents in the United States and Mexico may have higher rates of tobacco experimentation than other ethnic groups, possibly due to cultural factors and parental influences. This study examined three parental behaviors that may prompt smoking in children in Grades 3, 5, 7, and 9 in Tijuana. Mexico. Surveys were administered to 758 students in randomly selected classes in randomly selected schools in Tijuana. The most frequent prompt was the smoking parent asking the child to buy cigarettes (about two thirds), whereas about 60% asked the child to light the parent's cigarette, and about 20% of smoking parents asked the child to place the cigarette in his or her mouth to light it. Rates of prompting were very low among third graders but increased by Grade 5. Mother's smoking was associated with higher rates of all three types of parental prompting.