Prevalence of non-communicable diseases among household contacts of people with tuberculosis: A systematic review and individual participant data meta-analysis.

OBJECTIVE: To investigate the prevalence of non-communicable diseases among household contacts of people with tuberculosis. METHODS: We conducted a systematic review and individual participant data meta-analysis. We searched Medline, Embase and the Global Index Medicus from inception to 16 May 2023. We included studies that assessed for at least one non-communicable disease among household contacts of people with clinical tuberculosis. We estimated the non-communicable disease prevalence through mixed effects logistic regression for studies providing individual participant data, and compared it with estimates from aggregated data meta-analyses. Furthermore, we compared age and sex-standardised non-communicable disease prevalence with national-level estimates standardised for age and sex. RESULTS: We identified 39 eligible studies, of which 14 provided individual participant data (29,194 contacts). Of the remaining 25 studies, 18 studies reported aggregated data suitable for aggregated data meta-analysis. In individual participant data analysis, the pooled prevalence of diabetes in studies that undertook biochemical testing was 8.8% (95% confidence interval [CI], 5.1%-14.9%, four studies). Age-and sex-standardised prevalence was higher in two studies (10.4% vs. 6.9% and 11.5% vs. 8.4%) than the corresponding national estimates and similar in two studies. Prevalence of diabetes mellitus based on self-report or medical records was 3.4% (95% CI 2.6%-4.6%, 14 studies). Prevalence did not significantly differ compared to estimates from aggregated data meta-analysis. There were limited data for other non-communicable diseases. CONCLUSION: The prevalence of diabetes mellitus among household contacts was high while that of known diabetes was substantially lower, suggesting the underdiagnosis. tuberculosis household contact investigation offers opportunities to deliver multifaceted interventions to identify tuberculosis infection and disease, screen for non-communicable diseases and address shared risk factors.

Practical lessons learned from real-world implementation of the molecular classification for endometrial carcinoma.

OBJECTIVES: This study aimed to explore the practical organisational aspects and difficulties in the implementation of the molecular classification of endometrial carcinoma (EC), and to demonstrate its potential impact in prognostic risk group classification. METHODS: We conducted a multicentre, retrospective cohort study of 230 patients with EC diagnosed between 2019 and 2022. Sample processing, clinicopathological, treatment and follow-up data were collected. Molecular classification was obtained by p53 and mismatch repair proteins immunohistochemistry, and POLE next-generation sequencing. RESULTS: Implementation was achieved through centralization of molecular analysis. In practice, it was possible to optimise turnaround times of complete integrative reports for hysterectomy specimens to a median time of 18 workdays. If genetic study was started in endometrial biopsies before surgery, 82.0% were available at the time of multidisciplinary tumour board, compared to 8.4% if performed in hysterectomy. ECs were classified as follows: 37.8% no specific molecular profile, 31.7% p53 abnormal, 24.3% mismatch repair deficient, and 6.1% POLE mutant. Integration of these results with traditional clinicopathologic factors led to a change in prognostic risk group in 15 (6.5%) patients, most being initially allocated to high-intermediate (n = 8) and low (n = 5) risk groups. Eight patients changed to a higher risk, and 7 to a lower risk group, whereas 2 remained in the same group. CONCLUSIONS: Centralization of EC molecular classification is a feasible option for countries with limited resources. Optimization of workflows may be achieved by earlier analysis in biopsies and prioritisation of patients whose results imply changes in risk group classification.

Systematic Review and Meta-analyses of the Effect of Chemotherapy on Pulmonary Mycobacterium abscessus Outcomes and Disease Recurrence.

In pharmacokinetic/pharmacodynamic models of pulmonary Mycobacterium abscessus complex, the recommended macrolide-containing combination therapy has poor kill rates. However, clinical outcomes are unknown. We searched the literature for studies published between 1990 and 2017 that reported microbial outcomes in patients treated for pulmonary M. abscessus disease. A good outcome was defined as sustained sputum culture conversion (SSCC) without relapse. Random effects models were used to pool studies and estimate proportions of patients with good outcomes. Odds ratios (OR) and 95% confidence intervals (CI) were computed. Sensitivity analyses and metaregression were used to assess the robustness of findings. In 19 studies of 1,533 patients, combination therapy was administered to 508 patients with M. abscessus subsp. abscessus, 204 with M. abscessus subsp. massiliense, and 301 with M. abscessus with no subspecies specified. Macrolide-containing regimens achieved SSCC in only 77/233 (34%) new M. abscessus subsp. abscessus patients versus 117/141 (54%) M. abscessus subsp. massiliense patients (OR, 0.108 [95% CI, 0.066 to 0.181]). In refractory disease, SSCC was achieved in 20% (95% CI, 7 to 36%) of patients, which was not significantly different across subspecies. The estimated recurrent rates per month were 1.835% (range, 1.667 to 3.196%) for M. abscessus subsp. abscessus versus 0.683% (range, 0.229 to 1.136%) for M. abscessus subsp. massiliense (OR, 6.189 [95% CI, 2.896 to 13.650]). The proportion of patients with good outcomes was 52/223 (23%) with M. abscessus subsp. abscessus versus 118/141 (84%) with M. abscessus subsp. massiliense disease (OR, 0.059 [95% CI, 0.034 to 0.101]). M. abscessus subsp. abscessus pulmonary disease outcomes with the currently recommended regimens are atrocious, with outcomes similar to those for extensively drug-resistant tuberculosis. Therapeutically, the concept of nontuberculous mycobacteria is misguided. There is an urgent need to craft entirely new treatment regimens.

Clofazimine Prevents the Regrowth of Mycobacterium abscessus and Mycobacterium avium Type Strains Exposed to Amikacin and Clarithromycin.

Multidrug therapy is a standard practice when treating infections by nontuberculous mycobacteria (NTM), but few treatment options exist. We conducted this study to define the drug-drug interaction between clofazimine and both amikacin and clarithromycin and its contribution to NTM treatment. Mycobacterium abscessus and Mycobacterium avium type strains were used. Time-kill assays for clofazimine alone and combined with amikacin or clarithromycin were performed at concentrations of 0.25× to 2× MIC. Pharmacodynamic interactions were assessed by response surface model of Bliss independence (RSBI) and isobolographic analysis of Loewe additivity (ISLA), calculating the percentage of statistically significant Bliss interactions and interaction indices (I), respectively. Monte Carlo simulations with predicted human lung concentrations were used to calculate target attainment rates for combination and monotherapy regimens. Clofazimine alone was bacteriostatic for both NTM. Clofazimine-amikacin was synergistic against M. abscessus (I = 0.41; 95% confidence interval [CI], 0.29 to 0.55) and M. avium (I = 0.027; 95% CI, 0.007 to 0.048). Based on RSBI analysis, synergistic interactions of 28.4 to 29.0% and 23.2 to 56.7% were observed at 1× to 2× MIC and 0.25× to 2× MIC for M. abscessus and M. avium, respectively. Clofazimine-clarithromycin was also synergistic against M. abscessus (I = 0.53; 95% CI, 0.35 to 0.72) and M. avium (I = 0.16; 95% CI, 0.04 to 0.35), RSBI analysis showed 23.5% and 23.3 to 53.3% at 2× MIC and 0.25× to 0.5× MIC for M. abscessus and M. avium, respectively. Clofazimine prevented the regrowth observed with amikacin or clarithromycin alone. Target attainment rates of combination regimens were >60% higher than those of monotherapy regimens for M. abscessus and M. avium. The combination of clofazimine with amikacin or clarithromycin was synergistic in vitro. This suggests a potential role for clofazimine in treatment regimens that warrants further evaluation.

Failure of the Amikacin, Cefoxitin, and Clarithromycin Combination Regimen for Treating Pulmonary Mycobacterium abscessus Infection.

In a hollow-fiber model, we mimicked the drug exposures achieved in the lungs of humans treated with standard amikacin, clarithromycin, and cefoxitin combination therapy for Mycobacterium abscessus infection. At optimal dosing, a kill rate of -0.09 (95% confidence interval, -0.04 to 0.03) log10 CFU per ml/day was achieved over the first 14 days, after which there was regrowth due to acquired drug resistance. Thus, the standard regimen quickly failed. A new regimen is needed.

Moxifloxacin's Limited Efficacy in the Hollow-Fiber Model of Mycobacterium abscessus Disease.

Current regimens used to treat pulmonary Mycobacterium abscessus disease have limited efficacy. There is an urgent need for new drugs and optimized combinations and doses. We performed hollow-fiber-system studies in which M. abscessus was exposed to moxifloxacin lung concentration-time profiles similar to human doses of between 0 and 800 mg/day. The minimum bactericidal concentration and MIC were 8 and 2 mg/liter, respectively, in our M. abscessus strain, suggesting bactericidal activity. Measurement of the moxifloxacin concentrations in each hollow-fiber system revealed an elimination rate constant (kel) of 0.11 ± 0.05 h(-1) (mean ± standard deviation) (half-life of 9.8 h). Inhibitory sigmoid maximal effect (Emax) modeling revealed that the highest Emax was 3.15 ± 1.84 log10 CFU/ml on day 3, and the exposure mediating 50% of Emax (EC50) was a 0- to 24-h area under the concentration time curve (AUC0-24)-to-MIC ratio of 41.99 ± 31.78 (r(2) = 0.99). The EC80 was an AUC0-24/MIC ratio of 102.11. However, no moxifloxacin concentration killed the bacteria to burdens below the starting inoculum. There was regrowth beyond day 3 in all doses, with replacement by a resistant subpopulation that had an MIC of >32 mg/liter by the end of the experiment. A quadratic function best described the relationship between the AUC0-24/MIC ratio and the moxifloxacin-resistant subpopulation. Monte Carlo simulations of 10,000 patients revealed that the 400- to 800-mg/day doses would achieve or exceed the EC80 in ≤12.5% of patients. The moxifloxacin susceptibility breakpoint was 0.25 mg/liter, which means that almost all M. abscessus clinical strains are moxifloxacin resistant by these criteria. While moxifloxacin's efficacy against M. abscessus was poor, formal combination therapy studies with moxifloxacin are still recommended.

Tigecycline Is Highly Efficacious against Mycobacterium abscessus Pulmonary Disease.

Mycobacterium abscessus causes chronic pulmonary infections that are extremely difficult to cure. The currently recommended combination therapy is associated with high failure rates and relapse. Tigecycline has been explored in salvage regimens, with a response rate of 43% in those who received at least a month of therapy. We performed a dose-response study in a hollow-fiber system model of pulmonary M. abscessus infection in which we recapitulated tigecycline human pulmonary concentration-time profiles of 8 different doses for 21 days. We identified the maximal kill or efficacy in CFU per milliliter and the ratio of the 0- to 24-h area under the concentration-time curve to MIC (AUC/MIC) associated with 80% efficacy (EC80). The tigecycline efficacy was 5.38 ± 2.35 log10 CFU/ml, and the drug achieved the unprecedented feat of a bacterial level of 1.0 log10 CFU/ml below the pretreatment inoculum (1-log kill) of M. abscessus in the hollow-fiber system. The EC80 AUC/MIC ratio was 36.65, while that for a 1-log kill was 44.6. Monte Carlo experiments with 10,000 patients were used to identify the clinical dose best able to achieve the EC80 or 1-log kill. The standard dose of 100 mg/day had a cumulative fraction of response of 51% for the EC80 and 46% for 1-log kill. For both the EC80 target and 1-log kill, the optimal tigecycline clinical dose was identified as 200 mg/day. The susceptibility breakpoint was ≤0.5 mg/liter. Tigecycline is the most active single agent evaluated to date, and we propose that 200 mg/day be examined as the backbone of new combination therapy regimens to replace current treatment.

Genotypic Analysis of Genes Associated with Independent Resistance and Cross-Resistance to Isoniazid and Ethionamide in Mycobacterium tuberculosis Clinical Isolates.

Ethionamide (ETH) is an antibiotic used for the treatment of multidrug-resistant (MDR) tuberculosis (TB) (MDR-TB), and its use may be limited with the emergence of resistance in the Mycobacterium tuberculosis population. ETH resistance in M. tuberculosis is phenomenon independent or cross related when accompanied with isoniazid (INH) resistance. In most cases, resistance to INH and ETH is explained by mutations in the inhA promoter and in the following genes: katG, ethA, ethR, mshA, ndh, and inhA. We sequenced the above genes in 64 M. tuberculosis isolates (n = 57 ETH-resistant MDR-TB isolates; n = 3 ETH-susceptible MDR-TB isolates; and n = 4 fully susceptible isolates). Each isolate was tested for susceptibility to first- and second-line drugs using the agar proportion method. Mutations were observed in ETH-resistant MDR-TB isolates at the following rates: 100% in katG, 72% in ethA, 45.6% in mshA, 8.7% in ndh, and 33.3% in inhA or its promoter. Of the three ETH-susceptible MDR-TB isolates, all showed mutations in katG; one had a mutation in ethA, and another, in mshA and inhA. Finally, of the four fully susceptible isolates, two showed no detectable mutation in the studied genes, and two had mutations in mshA gene unrelated to the resistance. Mutations not previously reported were found in the ethA, mshA, katG, and ndh genes. The concordance between the phenotypic susceptibility testing to INH and ETH and the sequencing was 1 and 0.45, respectively. Among isolates exhibiting INH resistance, the high frequency of independent resistance and cross-resistance with ETH in the M. tuberculosis isolates suggests the need to confirm the susceptibility to ETH before considering it in the treatment of patients with MDR-TB.

Amikacin Pharmacokinetics/Pharmacodynamics in a Novel Hollow-Fiber Mycobacterium abscessus Disease Model.

The treatment of pulmonary Mycobacterium abscessus disease is associated with very high failure rates and easily acquired drug resistance. Amikacin is the key drug in treatment regimens, but the optimal doses are unknown. No good preclinical model exists to perform formal pharmacokinetics/pharmacodynamics experiments to determine these optimal doses. We developed a hollow-fiber system model of M. abscessus disease and studied amikacin exposure effects and dose scheduling. We mimicked amikacin human pulmonary pharmacokinetics. Both amikacin microbial kill and acquired drug resistance were linked to the peak concentration-to-MIC ratios; the peak/MIC ratio associated with 80% of maximal kill (EC80) was 3.20. However, on the day of the most extensive microbial kill, the bacillary burden did not fall below the starting inoculum. We performed Monte Carlo simulations of 10,000 patients with pulmonary M. abscessus infection and examined the probability that patients treated with one of 6 doses from 750 mg to 4,000 mg would achieve or exceed the EC80. We also examined these doses for the ability to achieve a cumulative area under the concentration-time curve of 82,232 mg · h/liter × days, which is associated with ototoxicity. The standard amikacin doses of 750 to 1,500 mg a day achieved the EC80 in ≤ 21% of the patients, while a dose of 4 g/day achieved this in 70% of the patients but at the cost of high rates of ototoxicity within a month or two. The susceptibility breakpoint was an MIC of 8 to 16 mg/liter. Thus, amikacin, as currently dosed, has limited efficacy against M. abscessus. It is urgent that different antibiotics be tested using our preclinical model and new regimens developed.

Time-kill kinetics of antibiotics active against rapidly growing mycobacteria.

OBJECTIVES: This study was conducted to generate basic pharmacodynamic information on the relationship between antibiotic concentrations and the growth of rapidly growing mycobacteria (RGM), and thereby contribute to a better understanding of current and future drug regimens for diseases caused by RGM. METHODS: Type strains of Mycobacterium abscessus and Mycobacterium fortuitum were used; the MICs of cefoxitin, amikacin, moxifloxacin, linezolid and clarithromycin were determined by broth microdilution. Time-kill assays were performed, exposing the bacteria to 2-fold concentrations from 0.25 to 32 times the MIC at 30°C for 120 h. The sigmoid maximum effect (Emax) model was fitted to the time-kill curves data. RESULTS: The highest killing of M. abscessus was observed between 24 and 72 h; amikacin had the highest Emax (0.0427 h(-1)), followed by clarithromycin (0.0231 h(-1)) and cefoxitin (0.0142 h(-1)). For M. fortuitum, between 3 and 24 h, amikacin also showed the highest Emax (0.1933 h(-1)). There were no significant differences between the Hill's slopes determined for all the antibiotics tested against M. abscessus or M. fortuitum (P = 0.2213 and P = 0.2696, respectively). CONCLUSIONS: The total effect observed for all antibiotics was low and primarily determined by the Emax and not by the Hill's slope. The limited activity detected fits well with the poor outcome of antibiotic treatment for disease caused by RGM, particularly for M. abscessus. An evaluation of drug combinations will be the next step in understanding and improving current treatment standards.

Time-kill kinetics of slowly growing mycobacteria common in pulmonary disease.

OBJECTIVES: This study aimed to provide basic pharmacodynamic information for key antibiotics used to treat Mycobacterium avium and Mycobacterium xenopi pulmonary disease. METHODS: M. avium subspecies hominissuis IWGMT49 and M. xenopi ATCC 19250 type strains were used; the MICs of clarithromycin, amikacin and moxifloxacin were determined by broth microdilution. Time-kill assays were performed, exposing bacteria to 2-fold concentrations from 0.062× to 32× the MIC at 37°C for 240 h for M. avium or 42 days for M. xenopi. The sigmoid maximum effect (Emax) model was fitted to the time-kill curve data. RESULTS: Maximum killing of M. avium by amikacin was obtained between 24 and 120 h (0.0180 h(-1)) and was faster and higher than with clarithromycin (0.0109 h(-1)); however, regrowth and amikacin-resistant mutants were observed. Killing rates for M. xenopi were higher, 0.1533 h(-1) for clarithromycin and 0.1385 h(-1) for moxifloxacin, yet required 42 days. There were no significant differences between the Hill's slopes determined for all of the antibiotics tested against M. avium or M. xenopi (P = 0.9663 and P = 0.0844, respectively). CONCLUSIONS: The killing effect of amikacin and clarithromycin on M. avium subspecies hominissuis was low, although amikacin activity was higher than that of clarithromycin, supporting its role in a combined therapy. Clarithromycin and moxifloxacin may have similar activity within treatment regimens for M. xenopi disease. Future studies of in vitro and in vivo pharmacokinetic/pharmacodynamic interactions are needed to improve the current regimens to treat these two important slowly growing mycobacteria in pulmonary disease.

Predictive value of molecular drug resistance testing of Mycobacterium tuberculosis isolates in Valle del Cauca, Colombia.

Previous evaluations of the molecular GenoType tests have promoted their use to detect resistance to first- and second-line antituberculosis drugs in different geographical regions. However, there are known geographic variations in the mutations associated with drug resistance in Mycobacterium tuberculosis, and especially in South America, there is a paucity of information regarding the frequencies and types of mutations associated with resistance to first- and second-line antituberculosis drugs. We therefore evaluated the performance of the GenoType kits in this region by testing 228 M. tuberculosis isolates in Colombia, including 134 resistant and 94 pansusceptible strains. Overall, the sensitivity and specificity of the GenoType MTBDRplus test ranged from 92 to 96% and 97 to 100%, respectively; the agreement index was optimal (Cohen's kappa, >0.8). The sensitivity of the GenoType MTBDRsl test ranged from 84 to 100% and the specificity from 88 to 100%. The most common mutations were katG S315T1, rpoB S531L, embB M306V, gyrA D94G, and rrs A1401G. Our results reflect the utility of the GenoType tests in Colombia; however, as some discordance still exists between the conventional and molecular approaches in resistance testing, we adhere to the recommendation that the GenoType tests serve as early guides for therapy, followed by phenotypic drug susceptibility testing for all cases.

[Long-Term Reversible Contraception in Adolescence: The Reality of a Tertiary Pediatric Hospital in Portugal]. / Contraceção Reversível de Longa Duração na Adolescência: A Realidade de um Hospital Pediátrico Terciário em Portugal.

INTRODUCTION: Contraception in adolescence is essential to prevent unwanted pregnancies, abortion and sexually transmitted diseases. The use of longacting reversible contraceptive methods (LARCs) has been highly recommended due to their efficacy since they are user independent methods. The aim of this study was to evaluate the use of LARCs in adolescence in the population of a Childhood and Adolescence Gynecology clinic, and to describe the sociodemographic characteristics of the adolescents as well as previous contraceptive practices. MATERIAL AND METHODS: Retrospective analysis that included adolescents using LARCs, monitored in a Childhood and Adolescence Gynecology clinic of a Portuguese tertiary pediatric hospital, between June 2012 and June 2021. RESULTS: A total of 122 adolescents were included, with a median age of 16 (11 - 18) years and 62.3% (n = 76) were sexually active. The preferred method was the subcutaneous implant, placed in 82.3% (n = 101), followed by the Levonorgestrel-Intrauterine System in 16.4% (n = 20) and the copper intrauterine device in 1.3% (n = 1). The main indications for LARCs were contraceptive needs 90.2% (n = 110), abnormal uterine bleeding during puberty in 14.8% (n = 18), dysmenorrhea in 10.7% (n = 13) and need for amenorrhea in 0.8% (n = 1). The median time of implant use was 20 (1 - 48) months and of the LNG-IUS it was 20 (1 - 36) months. The 12-month adherence rate for both was 76.2% (n = 93). The removal rate for reasons besides the expiration date was 9.8% (n = 12) in adolescents who had implants, and no LNG-IUS or copper intrauterine devices were removed. There were no pregnancies after insertion of LARCs. CONCLUSION: Contraceptive needs were the main reason for choosing LARCs, followed by abnormal uterine bleeding during puberty management and dysmenorrhea. All these factors may contribute to the high rate of satisfaction and continuity of these methods.

Introdução: A contraceção na adolescência tem um papel fundamental na sociedade por prevenir gravidezes indesejadas e infeções sexualmente transmissíveis. O uso de métodos contracetivos reversíveis de longa duração (LARCs) tem vindo a ser recomendado pela sua eficácia e perfil de segurança nesta faixa etária. O objetivo deste estudo foi avaliar a utilização de LARCs na população de uma consulta de Ginecologia da Infância e Adolescência e descrever as características sociodemográficas das adolescentes assim como a prática contracetiva prévia. Material e Métodos: Análise retrospetiva que incluiu as adolescentes utilizadoras de LARCs, acompanhadas na consulta de Ginecologia da Infância e Adolescência de um hospital pediátrico terciário português, no período entre junho de 2012 e junho de 2021. Resultados: Foram incluídas 122 adolescentes, cuja mediana de idades foi 16 (11 ­ 18) anos. Destas, 62,3% (n = 76) eram sexualmente ativas. O método preferencial foi o implante subcutâneo, colocado em 82,3% (n = 101), seguido do sistema intrauterino de Levonorgestrel (SIU-LNG) em 16,4% (n = 20) e o dispositivo intrauterino de cobre em 1,3% (n = 1). As principais indicações para a escolha de LARCs foram desejo contracetivo em 90,2% (n = 110), hemorragia uterina anormal da puberdade em 14,8% (n = 18), dismenorreia em 10,7% (n = 13) e necessidade de amenorreia em 0,8% (n = 1). O tempo mediano de utilização do implante foi 20 (1 ­ 48) meses e do SIU-LNG 20 (1 ­ 36) meses. A taxa de continuidade aos 12 meses para ambos foi de 76,2% (n = 93). A taxa de remoção antes do tempo padronizado foi de 9,8% (n = 12) nas adolescentes que colocaram implante, sendo que não foram removidos SIU-LNG ou dispositivo intrauterino de cobre. Não se registaram gravidezes após a colocação de LARCs. Conclusão: O desejo contracetivo foi o primeiro motivo para a escolha de um LARC seguido do controlo da hemorragia uterina anormal e da dismenorreia. Todos estes fatores poderão contribuir para a elevada taxa de satisfação e continuidade destes métodos.

Exploring stakeholders perspectives on TB contact investigation in Cali, Colombia: a qualitative study.

Introduction: Contact investigation is a proven intervention for tuberculosis (TB) case finding and prevention. Although widely endorsed by national public health authorities and the World Health Organization, many countries struggle to implement it effectively. The objective of the study is to describe and characterize the barriers and facilitators of TB contact investigation in Cali, Colombia from the perspective and experience of the key stakeholders involved. Methods: We collected data from group discussions during two workshop sessions with clinic and public health staff involved in TB contact investigation (June 2019 and March 2020 respectively) and semi-structured interviews with TB cases and their household contacts (July 2019 to April 2020). We undertook an inductive thematic analysis with the RADaR technique to characterize the barriers and facilitators of the TB contact investigation process. Results: The two workshops included 21 clinics and 12 public health staff. We also conducted 26 semi-structured interviews with TB cases and their household contacts. Using thematic analysis, we identified four common themes: Healthcare Operations, Essential Knowledge, Time Limitations and Competing Responsibilities, and Interpersonal Interactions. The main barriers to conducting household visits were low data quality, stigma and mistrust, safety concerns for health workers, and limited resources. The main barriers to TB uptake by contacts were competing responsibilities, low TB risk perceptions among contacts, and difficulty accessing diagnostic tests for contacts. In contrast, good communication and social skills among health workers and accurate TB knowledge facilitated successful household visits and TB test uptake, according to key stakeholders. Conclusion: This study provides a deeper understanding of TB contact investigation barriers and facilitators in a high-prevalence urban setting in a middle-income country from the perspective and experience of key stakeholders. The study shed light on the barriers that hinder household contacts engagement and TB test uptake such as issues of systemic capacity and TB knowledge. Also, highlighted facilitators such as the importance of interpersonal communication skills among health workers in the public and private sector. The insights from this study can serve as a valuable resource for public health organizations seeking to enhance their contact investigation efforts and improve TB control in similar settings.

First Report of Acanthocheilonema reconditum Outbreak in Canines with Clinical Signs of Anemia from Southwestern Colombia.

Different nematodes affect canines, however Acanthocheilonema reconditum was considered mostly a non-pathogenic parasite. Climate change, animal migration, and other factors transformed the dynamics of vector-borne diseases, including filariasis. Since 2016, a sudden increase in the number of dogs with microfilaremia was reported by different veterinary centers in Cali, southwest Colombia. The objective of this study was to molecularly identify the etiologic agent of this filariasis outbreak detected in this city, using PCR−RFLP and evaluating dogs' clinical signs. From 2018−2019, canine filariasis cases were prospectively evaluated after a microscopic test, recruiting 82 cases and 43 healthy controls from 2971 samples. Acanthocheilonema reconditum (Nematoda, Onchocercidae) was identified in 61.3% of the cases (49/82) by PCR−RFLP. Sanger sequencing of the 5.8S ribosomal RNA gene and internal transcribed spacer-2 fragment was additionally performed on seven cases, confirming A. reconditum in all of them. The filariasis cases are statistically associated with male dogs who have clinical signs of anemia, low levels of hemoglobin and hematocrit (p < 0.0001), and high levels of plasma proteins (p < 0.001). This emerging canine disease constitutes an important public health concern among veterinarians and active surveillance is advised to explore its zoonotic potential.

Multidrug-resistant Mycobacterium tuberculosis, Southwestern Colombia.

Using spoligotyping, we identified 13 genotypes and 17 orphan types among 160 Mycobacterium tuberculosis isolates from patients in Valle del Cauca, Colombia. The Beijing genotype represented 15.6% of the isolates and was correlated with multidrug-resistant tuberculosis, female sex of the patients, and residence in Buenaventura and may represent a new public health threat.

[Clinical behavior of infection and disease caused by non-tuberculous mycobacteria in Latin America: Scoping review]. / Comportamiento clínico de la infección y enfermedad causada por micobacterias no tuberculosas en Latinoamérica: Revisión de alcance.

Reports of infection and/or disease caused by non-tuberculous mycobacteria (NTM) are becoming increasingly frequent. This scope review describes the epidemiological and clinical trend of infection/disease caused by NTM in Latin America. OVID MEDLINE, Embase and LILACS databases were explored for relevant articles. After filtering, we included 44 articles, representing an overall population of 2,826 subjects diagnosed with NTM infection and disease; the majority of the publications included subjects from Brazil and Colombia (75%), cross-sectional studies were the most common (36.6%), most subjects were male (61.3%) and the median age of subjects was 40.1 years. Disease by NTM was reported in 37 publications, extrapulmonary presentation was the most frequent (54%), main comorbidities were other pulmonary diseases, HIV, cystic fibrosis, diabetes and malnutrition, as reported in 13 studies; tuberculosis diagnosis previous to NTM disease was reported in 15 articles. Aesthetic procedures were reported in 12 articles while clinical procedures were reported in 3 articles. Several NTM species were reported, being Mycobacterium avium (52%), M. abscessus (34%), M. chelonae (18%), M. fortuitum (16%) and M. kansasii (9.1%) the most frequent. Culture and molecular testing were the main methods for diagnosis and identification. Scientific literature on NTM from Latin American countries is scarce. There is an urgent need to conduct studies on the frequency and clinical impact of NTM infections, in order to accurately identify the current morbidity and mortality associated with NTM in Latin American. It is also important to strengthen the local diagnostic capacity and the existing networks focused on studying NTM.

Cada vez son más frecuentes los reportes de aislamientos y enfermedades producidas por micobacterias no tuberculosas (MNT). Esta revisión de alcance describe el comportamiento epidemiológico y clínico de la infección y enfermedad por MNT en Latinoamérica. Se realizó la búsqueda en las bases de datos MEDLINE vía OVID, Embase y LILACS. Después de la depuración, se incluyeron 44 artículos que representaron una población global de 2826 sujetos, a quienes se les diagnosticó infección y enfermedad por MNT; la mayoría de las investigaciones incluyeron sujetos de Brasil y Colombia (75%); los estudios transversales fueron los más frecuentes (36,6%), el sexo masculino fue el más afectado (61,3%), mientras que la mediana de edad fue 40,1 años. En 37 artículos se reportó enfermedad por MNT, siendo la localización extrapulmonar (54%) la más frecuente; las principales comorbilidades fueron las enfermedades pulmonares, VIH/sida, fibrosis quística, diabetes y desnutrición, reportadas en 13 estudios; en 15 artículos se reportó tuberculosis previa al evento por MNT. En 12 artículos se evidenciaron procedimientos estéticos; en tres, procedimientos clínicos previos. Se reportó variedad de especies de MNT, siendo Mycobacterium avium (52%), M. abscessus (34%), M. chelonae (18%), M. fortuitum (16%) y M. kansasii (9,1%) las más frecuentes. El método más usado para diagnosticar e identificar la enfermedad por MNT fue el cultivo, recientemente se agregaron también las pruebas moleculares. La literatura científica latinoamericana sobre la infección/enfermedad por MNT es escasa. Es apremiante conducir estudios de frecuencia e impacto clínico y fortalecer la capacidad diagnóstica y las redes de organizaciones existentes enfocadas al estudio de micobacterias para conocer la verdadera morbimortalidad asociada a las MNT en Latinoamérica.

Incidental Finding of Extreme Elevation of Serum Alkaline Phosphatase in Pregnancy.

Increased levels of alkaline phosphatase (ALP) should alert us to changes in the liver, kidney, bone and malignancy. However, there is a physiological increase in pregnancy up to twice the upper limit. There has been a paucity of cases reporting extreme elevations of ALP in pregnancy. This is a case of an incidental pregnancy finding of a 24-fold increase in ALP in the third trimester (2877 U/L). The patient was kept under surveillance and ALP levels were monitored during the postpartum period. Literature suggests a correlation between ALP elevation and several perinatal complications, proposing it could represent an important tool in monitoring high-risk pregnancies and underlying placental damage. We report a case with no perinatal complications and normal labor at term, with a placenta showing lesions of chronic villitis. We should not rely exclusively on an isolated, marked rise in ALP to dictate the approach in the absence of other fetomaternal considerations.

Evaluating the Quality of Tuberculosis Contact Investigation in Cali, Colombia: A Retrospective Cohort Study.

Tuberculosis (TB) contact investigation facilitates earlier TB diagnosis and initiation of preventive therapy, but little data exist about the quality of its implementation. We conducted a retrospective cohort study to evaluate processes of TB contact investigation for index TB patients diagnosed in Cali, Colombia, in 2017, including dropout at each stage and overall yield. We constructed multivariable models to identify predictors of completing 1) the baseline household visit and 2) a follow-up clinic visit for TB evaluation among referred contacts. Sixty-eight percent (759/1,120) of registered TB patients were eligible for contact investigation; 77% (582/759) received a household visit. Odds of completing a household visit were significantly lower among men (adjusted odds ratio [aOR]: 0.6; 95% CI: 0.4-0.9; P = 0.009) and patients living in Cali's western zone (aOR: 0.5; 95% CI: 0.3-0.8; P = 0.008). Among 1880 screened contacts, 31% (n = 582) met the criteria for clinic referral, 47% (n = 271) completed a clinic visit, and 85% (231/271) completed testing. After adjusting for clustering by index patient, odds of completing referral were higher among contacts with cough (aOR: 22; 95% CI: 7.1-66; P < 0.001) and contacts living in the western zone (aOR: 4.1; 95% CI: 1.2-15; P = 0.03). The cumulative probability of a symptomatic contact from an eligible household completing TB evaluation was only 28%. The yield of active TB patients among contacts was only 0.3% (5/1880). Only 16% (17/103) of children aged < 5 years and none of the eight persons living with HIV, reported preventive therapy initiation. Routine monitoring of process indicators may facilitate quality improvement to close gaps in contact tracing and increase yield.

Identification of Nontuberculous Mycobacteria in Drinking Water in Cali, Colombia.

Nontuberculous mycobacteria (NTM) are ubiquitous microorganisms naturally resistant to antibiotics and disinfectants that can colonize drinking water supply systems. Information regarding the spread of NTM in specifically South America and Colombia is limited. We aimed to identify and characterize NTM present in tap water samples from Cali, Colombia. Drinking water samples and faucet biofilm swabs were collected in 18 places, including the city's three main water treatment plants (WTPs). Filter-trapped material and eluates (0.45 µm) from swab washes were plated in 7H11 agar plates. Suspected colonies were evaluated microscopically, and NTM species were identified based on the rpoB gene. Antibiotic susceptibility testing was also performed. Fifty percent (9/18) of sampling points were positive for NTM (including two WTPs), from which 16 different isolates were identified: Mycobacterium mucogenicum (8/16), M. phocaicum (3/16), M. chelonae (2/16), M. mageritense (2/16), and M. fortuitum (1/16), all rapidly growing mycobacteria. A susceptibility profile was obtained from 68.75% (11/16) of the isolates. M. chelonae was the most resistant species. All NTM isolated are potentially responsible for human diseases; our findings might provide a baseline for exploring NTM transmission dynamics and clinical characterization, as well as potential associations between NTM species found in drinking water and isolates from patients.