Characterization of Drug-Resistant Lipid-Dependent Differentially Detectable Mycobacterium tuberculosis

An estimated 15-20% of patients who are treated for pulmonary tuberculosis (TB) are culture-negative at the time of diagnosis. Recent work has focused on the existence of differentially detectable Mycobacterium tuberculosis (Mtb) bacilli that do not grow under routine solid culture conditions without the addition of supplementary stimuli. We identified a cohort of TB patients in Lima, Peru, in whom acid-fast bacilli could be detected by sputum smear microscopy, but from whom Mtb could not be grown in standard solid culture media. When we attempted to re-grow Mtb from the frozen sputum samples of these patients, we found that 10 out of 15 could be grown in a glycerol-poor/lipid-rich medium. These fell into the following two groups: a subset that could be regrown in glycerol after lipid-resuscitation , and a group that displayed a heritable glycerol-sensitive phenotype that were unable to grow in the presence of this carbon source. Notably, all of the glycerol-sensitive strains were found to be multidrug resistant. Although whole-genome sequencing of the lipid-resuscitated strains identified 20 unique mutations compared to closely related strains, no single genetic lesion could be associated with this phenotype. In summary, we found that lipid-based media effectively fostered the growth of Mtb from a series of sputum smear-positive samples that were not culturable in glycerol-based Lowenstein-Jensen or 7H9 media, which is consistent with Mtb\u27s known preference for non-glycolytic sources during infection. Analysis of the recovered strains demonstrated that both genetic and non-genetic mechanisms contribute to the observed differential capturability, and suggested that this phenotype may be associated with drug resistance

Diagnostic Performance Assessment of Saliva RT-PCR and Nasopharyngeal Antigen for the Detection of SARS-CoV-2 in Peru

Widely available and reliable testing for SARS-CoV-2 is essential for the public health response to the COVID-19 pandemic. We estimated the diagnostic performance of reverse transcription PCR (RT-PCR) performed on saliva and the SD Biosensor STANDARD Q antigen test performed on nasopharyngeal swab compared to the reference standard, nasopharyngeal swab (NP) RT-PCR. We enrolled participants living and/or seeking care in health facilities in North Lima, Peru from November 2020 to January 2021. Consenting participants underwent same-day RT-PCR on both saliva and nasopharyngeal swab specimens, antigen testing on a nasopharyngeal swab specimen, pulse oximetry, and standardized symptom assessment. We calculated sensitivity, specificity, and predictive values for the nasopharyngeal antigen and saliva RT-PCR compared to nasopharyngeal RT-PCR. Of 896 participants analyzed, 567 (63.3%) had acute signs/symptoms of COVID-19. The overall sensitivity and specificity of saliva RT-PCR were 85.8% and 98.1%, respectively. Among participants with and without acute signs/symptoms of COVID-19, saliva sensitivity was 87.3% and 37.5%, respectively. Saliva sensitivity was 97.4% and 56.0% among participants with cycle threshold (CT) values of #30 and .30 on nasopharyngeal RT-PCR, respectively. The overall sensitivity and specificity of nasopharyngeal antigen were 73.2% and 99.4%, respectively. The sensitivity of the nasopharyngeal antigen test was 75.1% and 12.5% among participants with and without acute signs/symptoms of COVID-19, and 91.2% and 26.7% among participants with CT values of #30 and .30 on nasopharyngeal RT-PCR, respectively. Saliva RT-PCR achieved the WHO-recommended threshold of .80% for sensitivity for the detection of SARS-CoV-2, while the SD Biosensor nasopharyngeal antigen test did not. IMPORTANCE In this diagnostic validation study of 896 participants in Peru, saliva reverse transcription PCR (RT-PCR) had .80% sensitivity for the detection of SARS-CoV-2 among all-comers and symptomatic individuals, while the SD Biosensor STANDARD Q antigen test performed on nasopharyngeal swab had,80% sensitivity, except for participants whose same-day nasopharyngeal RT-PCR results showed cycle threshold values of,30, consistent with a high viral load in the nasopharynx. The specificity was high for both tests. Our results demonstrate that saliva sampling could serve as an alternative noninvasive technique for RT-PCR diagnosis of SARS-CoV-2. The role of nasopharyngeal antigen testing is more limited; when community transmission is low, it may be used for mass screenings among asymptomatic individuals with high testing frequency. Among symptomatic individuals, the nasopharyngeal antigen test may be relied upon for 4 to 8 days after symptom onset, or in those likely to have high viral load, whereupon it showed .80% sensitivity.Revisión por pare

High prevalence and heterogeneity of Dysglycemia in patients with tuberculosis from Peru: a prospective cohort study

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-10-29T11:51:28Z No. of bitstreams: 1 Calderon, R. High....pdf: 2042526 bytes, checksum: 3f541403ffb4892d058d895c77a33074 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-10-29T12:12:29Z (GMT) No. of bitstreams: 1 Calderon, R. High....pdf: 2042526 bytes, checksum: 3f541403ffb4892d058d895c77a33074 (MD5)Made available in DSpace on 2019-10-29T12:12:29Z (GMT). No. of bitstreams: 1 Calderon, R. High....pdf: 2042526 bytes, checksum: 3f541403ffb4892d058d895c77a33074 (MD5) Previous issue date: 2019-01-11Consejo Nacional de Ciencia, Tecnología e Innovación Tecnológica (CONCYTEC-Peru) / Fondo Nacional de Desarrollo Científico, Tecnológico y de Innovación Tecnológica (FONDECYT, Convenio 175–2015). The work from BBA was supported by intramural research program from FIOCRUZ, by the National Institutes of Health (U01AI115940 and U01AI069923) and by the Departamento de Ciência e Tecnologia (DECIT) - Secretaria de Ciência e Tecnologia (SCTIE) – Ministério da Saúde (MS), Brazil (25029.000507/2013–07). MBA receives a fellowship from the Fundação de Amparo à Pesquisa da Bahia (FAPESB). BBA is a senior scientist from the Conselho Nacional de Desenvolvimento Científico e Tecnológico.Socios en Salud Sucursal Peru. Lima, Peru / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Instituto Brasileiro para Investigação da Tuberculose. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil.Socios en Salud Sucursal Peru. Lima, Peru.Socios en Salud Sucursal Peru. Lima, Peru.Socios en Salud Sucursal Peru. Lima, Peru.Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil.Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brazil.Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Harvard Medical School / Department of Global Health and Social Medicine. Boston, MA, USA.Socios en Salud Sucursal Peru. Lima, Peru / Universidade Federal do Rio de Janeiro. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil / Universidade Federal da Bahia. Faculdade de Medicina. Salvador, BA, Brasil / Fundação José Silveira. Instituto Brasileiro para Investigação da Tuberculose. Salvador, BA, Brasil / Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil / Fundação José Silveira. Multinational Organization Network Sponsoring Translational and Epidemiological Research Initiative. Salvador, BA, Brasil / Faculdade de Tecnologia e Ciências. Curso de Medicina. Salvador, BA, Brasil / Universidade de Salvador. Salvador, BA, Brasil /Escola Bahiana de Medicina e Saúde Pública. Salvador, BA, Brasil.The accuracy of different laboratory tests for diagnosis of diabetes mellitus (DM) and prediabetes (preDM) in populations exposed to tuberculosis (TB) remains poorly understood. Here, we examined the prevalence of DM and preDM in TB affected people in Lima, Peru. Methods: A prospective cohort study of patients affected TB and their household contacts (HHC), was conducted between February and November 2017 in Lima, Peru. Fasting plasma glucose (FPG), HbA1c and oral glucose tolerance test (OGTT) were used to detect DM and preDM in a prospective cohort of TB patients (n = 136) and household contacts (n = 138). Diagnostic performance of the laboratory tests was analyzed. Potential effects of sociodemographic and clinical factors on detection of dysglycemia were analyzed. Results: In TB patients, prevalence of DM and preDM was 13.97 and 30.88% respectively. Lower prevalence of both DM (6.52%) and preDM (28.99%) were observed in contacts. FPG, HbA1c and OGTT had poor agreement in detection of preDM in either TB cases or contacts. TB-DM patients had substantially lower hemoglobin levels, which resulted in low accuracy of HbA1c-based diagnosis. Classic sociodemographic and clinical characteristics were not different between TB patients with or without dysglycemia. Conclusion: High prevalence of DM and preDM was found in both TB patients and contacts in Lima. Anemia was strongly associated with TB-DM, which directly affected the diagnostic performance of HbA1c in such population

Dysglycemia is associated with Mycobacterium tuberculosis lineages in tuberculosis patients of North Lima-Peru.

This study was performed to investigate the role of dysglycemia on the genetic diversity of Mycobacterium tuberculosis (MTB) among pulmonary tuberculosis (TB) patients to build scientific evidence about the possible mechanisms of TB transmission. MTB isolates obtained of patients affected by pulmonary tuberculosis from health care facilities of North Lima-Peru, were analyzed using whole genome sequencing and 24-locus mycobacterial interspersed repetitive-unit -variable-number tandem repeats (MIRU-VNTR). Subsequently, clinical and epidemiological characteristics were associated with clustering, lineages and comorbid conditions. The analysis carried out 112 pulmonary TB patients from various health centers in North Lima, 17 (15%) had diabetes mellitus (DM) and 33 (29%) had pre-diabetes (PDM). Latin American-Mediterranean, Haarlem and Beijing were the most frequent MTB lineages found in those patients. Previous TB (adjusted odds ratio [aOR] = 3.65; 95%CI: 1.32-17.81), age (aOR = 1.12; 95%CI: 1.03-1.45) and Beijing lineage (aOR = 3.53; 95%CI: 1.08-13.2) were associated with TB-DM comorbidity. Alcoholism (aOR = 2.92; 95%CI: 1.10-8.28), age (aOR = 1.05; 95%CI: 1.03-1.12) and Haarlem lineage (aOR = 2.54; 95%CI: 1.04-6.51) were associated with TB-PDM comorbidity. Beijing and Haarlem lineages were independently associated with TB-DM and TB-PDM comorbidities, respectively. Although these findings may be surprising, we must be cautious to suggest that dysglycemia could be associated with a highly clustering and predisposition of MTB lineages related to a serious impact on the severity of TB disease, which requires further research

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Evaluation of a quality improvement intervention to reduce anastomotic leak following right colectomy (EAGLE): pragmatic, batched stepped-wedge, cluster-randomized trial in 64 countries

Background Anastomotic leak affects 8 per cent of patients after right colectomy with a 10-fold increased risk of postoperative death. The EAGLE study aimed to develop and test whether an international, standardized quality improvement intervention could reduce anastomotic leaks. Methods The internationally intended protocol, iteratively co-developed by a multistage Delphi process, comprised an online educational module introducing risk stratification, an intraoperative checklist, and harmonized surgical techniques. Clusters (hospital teams) were randomized to one of three arms with varied sequences of intervention/data collection by a derived stepped-wedge batch design (at least 18 hospital teams per batch). Patients were blinded to the study allocation. Low- and middle-income country enrolment was encouraged. The primary outcome (assessed by intention to treat) was anastomotic leak rate, and subgroup analyses by module completion (at least 80 per cent of surgeons, high engagement; less than 50 per cent, low engagement) were preplanned. Results A total 355 hospital teams registered, with 332 from 64 countries (39.2 per cent low and middle income) included in the final analysis. The online modules were completed by half of the surgeons (2143 of 4411). The primary analysis included 3039 of the 3268 patients recruited (206 patients had no anastomosis and 23 were lost to follow-up), with anastomotic leaks arising before and after the intervention in 10.1 and 9.6 per cent respectively (adjusted OR 0.87, 95 per cent c.i. 0.59 to 1.30; P = 0.498). The proportion of surgeons completing the educational modules was an influence: the leak rate decreased from 12.2 per cent (61 of 500) before intervention to 5.1 per cent (24 of 473) after intervention in high-engagement centres (adjusted OR 0.36, 0.20 to 0.64; P < 0.001), but this was not observed in low-engagement hospitals (8.3 per cent (59 of 714) and 13.8 per cent (61 of 443) respectively; adjusted OR 2.09, 1.31 to 3.31). Conclusion Completion of globally available digital training by engaged teams can alter anastomotic leak rates. Registration number: NCT04270721 (http://www.clinicaltrials.gov)

Global variation in postoperative mortality and complications after cancer surgery: a multicentre, prospective cohort study in 82 countries

© 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licenseBackground: 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods: This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov, NCT03471494. Findings: Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation: Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding: National Institute for Health Research Global Health Research Unit

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research