Tuberculosis (TB) destroys lung tissues and this immunopathology is mediated in part by Matrix Metalloproteinases (MMPs). There are no data on the relationship between local tissue MMPs ...concentrations, anti-tuberculosis therapy and sputum conversion.
Induced sputum was collected from 68 TB patients and 69 controls in a cross-sectional study. MMPs concentrations were measured by Luminex array, TIMP concentrations by ELISA and were correlated with a disease severity score (TBscore). 46 TB patients were then studied longitudinally at the 2nd, 8th week and end of treatment.
Sputum MMP-1,-2,-3,-8,-9 and TIMP-1 and -2 concentrations are increased in TB. Elevated MMP-1 and -3 concentrations are independently associated with higher TB severity scores (p<0.05). MMP-1, -3 and -8 concentrations decreased rapidly during treatment (p<0.05) whilst there was a transient increase in TIMP-1/2 concentrations at week 2. MMP-2, -8 and -9 and TIMP-2 concentrations were higher at TB diagnosis in patients who remain sputum culture positive at 2 weeks and MMP-3, -8 and TIMP-1 concentrations were higher in these patients at 2nd week of TB treatment.
MMPs are elevated in TB patients and associate with disease severity. This matrix-degrading phenotype resolves rapidly with treatment. The MMP profile at presentation correlates with a delayed treatment response.
Worldwide, nations have struggled during the coronavirus disease 2019 (COVID‐19) pandemic. However, Latin America and the Caribbean faced an unmatched catastrophic toll. As of March 2022, the region ...has reported approximately 15% of cases and 28% of deaths worldwide. Considering the relatively late arrival of SARS‐CoV‐2, several factors in the region were determinants of the humanitarian crisis that ensued. Pandemic unpreparedness, fragile healthcare systems, forthright inequalities, and poor governmental support facilitated the spread of the virus throughout the region. Moreover, reliance on repurposed and ineffective drugs such as hydroxychloroquine and ivermectin—to treat or prevent COVID‐19—was publicised through misinformation and created a false sense of security and poor adherence to social distancing measures. While there were hopes that herd immunity could be achieved after the region's disastrous first peak, the emergence of the Gamma, Lambda, and Mu variants made this unattainable. This review explores how Latin America and the Caribbean fared during the first 2 years of the pandemic, and how, despite all the challenges, the region became a global leader in COVID‐19 vaccination, with 63% of its population fully vaccinated.
Carrion's disease affects small Andean communities in Peru, Colombia and Ecuador and is characterized by two distinct disease manifestations: an abrupt acute bacteraemic illness (Oroya fever) and an ...indolent cutaneous eruptive condition (verruga Peruana). Case fatality rates of untreated acute disease can exceed 80% during outbreaks. Despite being an ancient disease that has affected populations since pre-Inca times, research in this area has been limited and diagnostic and treatment guidelines are based on very low evidence reports. The apparently limited geographical distribution and ecology of Bartonella bacilliformis may present an opportunity for disease elimination if a clear understanding of the epidemiology and optimal case and outbreak management can be gained.
All available databases were searched for English and Spanish language articles on Carrion's disease. In addition, experts in the field were consulted for recent un-published work and conference papers. The highest level evidence studies in the fields of diagnostics, treatment, vector control and epidemiology were critically reviewed and allocated a level of evidence, using the Oxford Centre for Evidence-Based Medicine (CEBM) guidelines.
A total of 44 studies were considered to be of sufficient quality to be included in the analysis. The majority of these were level 4 or 5 (low quality) evidence and based on small sample sizes. Few studies had been carried out in endemic areas.
Current approaches to the diagnosis and management of Carrion's disease are based on small retrospective or observational studies and expert opinion. Few studies take a public health perspective or examine vector control and prevention. High quality studies performed in endemic areas are required to define optimal diagnostic and treatment strategies.
In order to generate independent performance data regarding accuracy of COVID-19 antigen-based rapid diagnostic tests (Ag-RDTs), prospective diagnostic evaluation studies across multiple sites are ...required to evaluate their performance in different clinical settings. This report describes the clinical evaluation the GENEDIA W COVID-19 Ag Device (Green Cross Medical Science Corp., Chungbuk, Korea) and the ActiveXpress+ COVID-19 Complete Testing Kit (Edinburgh Genetics Ltd, UK), in two testing sites Peru and the United Kingdom.
Nasopharyngeal swabs collected from 456 symptomatic patients at primary points of care in Lima, Peru and 610 symptomatic participants at a COVID-19 Drive-Through testing site in Liverpool, England were analyzed by Ag-RDT and compared to RT-PCR. Analytical evaluation of both Ag-RDTs was assessed using serial dilutions of direct culture supernatant of a clinical SARS-CoV-2 isolate from the B.1.1.7 lineage.
For GENEDIA brand, the values of overall sensitivity and specificity were 60.4% 95% CI 52.4-67.9%, and 99.2% 95% CI 97.6-99.7% respectively; and for Active Xpress+ the overall values of sensitivity and specificity were 66.2% 95% CI 54.0-76.5%, and 99.6% 95% CI 97.9-99.9% respectively. The analytical limit of detection was determined at 5.0 x 102 pfu/ml what equals to approximately 1.0 x 104 gcn/ml for both Ag-RDTs. The UK cohort had lower median Ct values compared to that of Peru during both evaluations. When split by Ct, both Ag-RDTs had optimum sensitivities at Ct<20 (in Peru; 95% 95% CI 76.4-99.1% and 100.0% 95% CI 74.1-100.0% and in the UK; 59.2% 95% CI 44.2-73.0% and 100.0% 95% CI 15.8-100.0%, for the GENDIA and the ActiveXpress+, respectively).
Whilst the overall clinical sensitivity of the Genedia did not meet WHO minimum performance requirements for rapid immunoassays in either cohort, the ActiveXpress+ did so for the small UK cohort. This study illustrates comparative performance of Ag-RDTs across two global settings and considers the different approaches in evaluation methods.
Depression is a common comorbidity of tuberculosis (TB) and is associated with poor adherence to treatment of multiple disorders. We conducted a systematic review to synthesize the existing evidence ...on the relationship between depression and negative outcomes of TB treatment.
We systematically reviewed studies that evaluated depressive symptoms (DS) directly or indirectly through psychological distress (PD) and measured negative treatment outcomes of drug-sensitive pulmonary TB, defined as death, loss to follow-up, or non-adherence. Sources included PubMed, Global Health Library, Embase, Scopus and Web of Science from inception to August 2019.
Of the 2,970 studies initially identified, eight articles were eligible for inclusion and two were used for the primary outcome meta-analysis. We found a strong association between DS and negative TB treatment outcomes (OR = 4.26; CI95%:2.33-7.79; I2 = 0%). DS were also associated with loss to follow-up (OR = 8.70; CI95%:6.50-11.64; I2 = 0%) and death (OR = 2.85; CI95%:1.52-5.36; I2 = 0%). Non-adherence was not associated with DS and PD (OR = 1.34; CI95%:0.70-2.72; I2 = 94.36) or PD alone (OR = 0.92; CI95%:0.81-1.05; I2 = 0%).
DS are associated with the negative TB treatment outcomes of death and loss to follow-up. Considerable heterogeneity exists in the definition of depression and outcomes such as non-adherence across the limited number of studies on this topic.
Proton-pump inhibitors (PPIs) are among the most frequently prescribed medications. Community-acquired pneumonia (CAP) is a common cause of morbidity, mortality and healthcare spending. Some studies ...suggest an increased risk of CAP among PPI users. We conducted a systematic review and meta-analysis to determine the association between outpatient PPI therapy and risk of CAP in adults.
We conducted systematic searches of MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Scopus and Web of Science on February 3, 2014. Case-control studies, case-crossover, cohort studies and randomized controlled trials reporting outpatient PPI exposure and CAP diagnosis for patients ≥18 years old were eligible. Our primary outcome was the association between CAP and PPI therapy. A secondary outcome examined the risk of hospitalization for CAP and subgroup analyses evaluated the association between PPI use and CAP among patients of different age groups, by different PPI doses, and by different durations of PPI therapy.
Systematic review of 33 studies was performed, of which 26 studies were included in the meta-analysis. These 26 studies included 226,769 cases of CAP among 6,351,656 participants. We observed a pooled risk of CAP with ambulatory PPI therapy of 1.49 (95% CI 1.16, 1.92; I2 99.2%). This risk was increased during the first month of therapy (OR 2.10; 95% CI 1.39, 3.16), regardless of PPI dose or patient age. PPI therapy also increased risk for hospitalization for CAP (OR 1.61; 95% CI: 1.12, 2.31).
Outpatient PPI use is associated with a 1.5-fold increased risk of CAP, with the highest risk within the first 30 days after initiation of therapy. Providers should be aware of this risk when considering PPI use, especially in cases where alternative regimens may be available or the benefits of PPI use are uncertain.
Diabetes triples the risk for active tuberculosis, thus the increasing burden of type 2 diabetes will help to sustain the present tuberculosis epidemic. Recommendations have been made for ...bidirectional screening, but evidence is scarce about the performance of specific tuberculosis tests in individuals with diabetes, specific diabetes tests in patients with tuberculosis, and screening and preventive therapy for latent tuberculosis infections in individuals with diabetes. Clinical management of patients with both diseases can be difficult. Tuberculosis patients with diabetes have a lower concentration of tuberculosis drugs and a higher risk of drug toxicity than tuberculosis patients without diabetes. Good glycaemic control, which reduces long-term diabetes complications and could also improve tuberculosis treatment outcomes, is hampered by chronic inflammation, drug-drug interactions, suboptimum adherence to drug treatments, and other factors. Besides drug treatments for tuberculosis and diabetes, other interventions, such as education, intensive monitoring, and lifestyle interventions, might be needed, especially for patients with newly diagnosed diabetes or those who need insulin. From a health systems point of view, delivery of optimum care and integration of services for tuberculosis and diabetes is a huge challenge in many countries. Experience from the combined tuberculosis and HIV/AIDS epidemic could serve as an example, but more studies are needed that include economic assessments of recommended screening and systems to manage concurrent tuberculosis and diabetes.
Objective
To describe the characteristics and management of Diabetes mellitus (DM) patients from low‐ and middle‐income countries (LMIC).
Methods
We systematically characterised consecutive DM ...patients attending public health services in urban settings in Indonesia, Peru, Romania and South Africa, collecting data on DM treatment history, complications, drug treatment, obesity, HbA1c and cardiovascular risk profile; and assessing treatment gaps against relevant national guidelines.
Results
Patients (median 59 years, 62.9% female) mostly had type 2 diabetes (96%), half for >5 years (48.6%). Obesity (45.5%) and central obesity (females 84.8%; males 62.7%) were common. The median HbA1c was 8.7% (72 mmol/mol), ranging from 7.7% (61 mmol/mol; Peru) to 10.4% (90 mmol/mol; South Africa). Antidiabetes treatment included metformin (62.6%), insulin (37.8%), and other oral glucose‐lowering drugs (34.8%). Disease complications included eyesight problems (50.4%), EGFR <60 ml/min (18.9%), heart disease (16.5%) and proteinuria (14.7%). Many had an elevated cardiovascular risk with elevated blood pressure (36%), LDL (71.0%) and smoking (13%), but few were taking antihypertensive drugs (47.1%), statins (28.5%) and aspirin (30.0%) when indicated. Few patients on insulin (8.0%), statins (8.4%) and antihypertensives (39.5%) reached treatment targets according to national guidelines. There were large differences between countries in terms of disease profile and medication use.
Conclusion
DM patients in government clinics in four LMIC with considerable growth of DM have insufficient glycaemic control, frequent macrovascular and other complications, and insufficient preventive measures for cardiovascular disease. These findings underline the need to identify treatment barriers and secure optimal DM care in such settings.
Objectif
Décrire les caractéristiques et la prise en charge des patients atteints de diabète sucré (DS) dans les pays à revenu faible ou intermédiaire (PRFI).
Méthodes
Nous avons systématiquement caractérisé les patients atteints de DS visitant les services de santé publique en milieu urbain en Indonésie, au Pérou, en Roumanie et en Afrique du Sud, recueillant des données sur les antécédents de traitement du DS, les complications, le traitement médicamenteux, l'obésité, HbA1c, le profil de risque cardiovasculaire et évaluant les écarts de traitement par rapport aux directives nationales pertinentes.
Résultats
Les patients (médiane de 59 ans, 62,9% de femmes) avaient pour la plupart un diabète de type 2 (96%), la moitié depuis plus de 5 ans (48,6 %). L'obésité (45,5%) et l'obésité centrale (femmes 84,8%; hommes 62,7%) étaient fréquentes. Le taux moyen d'HbA1c était de 8,7% (72 mmol/mol), allant de 7,7% (61 mmol/mol, au Pérou) à 10,4% (90 mmol/mol, en Afrique du Sud). Le traitement antidiabétique comprenait la metformine (62,6%), l'insuline (37,8%) et d'autres hypoglycémiants oraux (34,8%). Les complications de la maladie comprenaient des troubles de la vue (50,4%), un EGFR <60 ml/min (18,9%), une cardiopathie (16,5%) et une protéinurie (14,7%). Bon nombre d'entre eux présentaient un risque cardiovasculaire élevé avec une pression artérielle élevée (36%) et un LDL élevé (71%) et le tabagisme (13%), mais peu d'entre eux prenaient des antihypertenseurs (47,1%), des statines (28,5%) et de l'aspirine (30,0%) lorsqu'indiqué. Peu de patients sous insuline (8,0%), statines (8,4%) et antihypertenseurs (39,5%) ont atteint les objectifs de traitement conformément aux directives nationales. Il y avait de grandes différences entre les pays en termes de profil de la maladie et d'utilisation des médicaments.
Conclusion
Les patients atteints de DS dans les cliniques publiques de quatre PRFI avec une augmentation considérable du DS présentent un contrôle glycémique insuffisant, de fréquentes complications macrovasculaires et autres et des mesures de prévention insuffisantes pour les maladies cardiovasculaires. Ces résultats soulignent la nécessité d'identifier les obstacles au traitement et d'obtenir des soins optimaux pour le DS dans de tels contextes.
Pulmonary cavities, the hallmark of tuberculosis (TB), are characterized by high mycobacterial load and perpetuate the spread of M. tuberculosis. The mechanism of matrix destruction resulting in ...cavitation is not well defined. Neutrophils are emerging as key mediators of TB immunopathology and their influx are associated with poor outcomes. We investigated neutrophil-dependent mechanisms involved in TB-associated matrix destruction using a cellular model, a cohort of 108 patients, and in separate patient lung biopsies. Neutrophil-derived NF-kB-dependent matrix metalloproteinase-8 (MMP-8) secretion was up-regulated in TB and caused matrix destruction both in vitro and in respiratory samples of TB patients. Collagen destruction induced by TB infection was abolished by doxycycline, a licensed MMP inhibitor. Neutrophil extracellular traps (NETs) contain MMP-8 and are increased in samples from TB patients. Neutrophils lined the circumference of human pulmonary TB cavities and sputum MMP-8 concentrations reflected TB radiological and clinical disease severity. AMPK, a central regulator of catabolism, drove neutrophil MMP-8 secretion and neutrophils from AMPK-deficient patients secrete lower MMP-8 concentrations. AMPK-expressing neutrophils are present in human TB lung biopsies with phospho-AMPK detected in nuclei. These data demonstrate that neutrophil-derived MMP-8 has a key role in the immunopathology of TB and is a potential target for host-directed therapy in this infectious disease.
Tuberculosis is one of the leading causes of death worldwide, primarily affecting low- and middle income countries and individuals with limited-resources within fractured health care systems. ...Unfortunately, the COVID-19 pandemic has only served to aggravate the already existing diagnostic gap, decreasing the number of people who get diagnosed and thereby complete successful treatment. In addition to this, comorbidities act as an external component that when added to the TB management equation, renders it even more complex. Among the various comorbidities that interact with TB disease, diabetes mellitus and depression are two of the most prevalent among non-communicable diseases within the TB population and merits a thoughtful consideration when the healthcare system provides care for them. TB patients with diabetes mellitus (TB-DM) or depression both have an increased risk of mortality, relapse and recurrence. Both of these diseases when in presence of TB present a ‘vicious-circle-like’ mechanism, meaning that the effect of each disease can negatively add up, in a synergistic manner, complicating the patient’s health state. Among TB-DM patients, high glucose blood levels can decrease the effectiveness of anti-tuberculosis drugs; however, higher doses of anti-tuberculous drugs could potentially decrease the effects of DM drugs. Among the TB-depression patients, not only do we have the adherence to treatment problems, but depression itself can biologically shift the immunological profile responsible for TB containment, and the other way around, TB itself can alter the hormonal balance of several neurotransmitters responsible for depression. In this paper, we review these and other important aspects such as the pharmacological interactions found in the treatment of TB-DM and TB-depression patients and the implication on TB care and pharmacological considerations.
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