Zhengfang Hu, Meng Zhou, Xin Jiang, Yaling Feng, Zhicheng Yu, Yuhao Li, Songhua Chen, Qian-Ge Wu, W. Wang, C. Horsburgh, Jr., Yu Zhang, Lina Zhou, Chonggao Hu, Kui Liu, Bin Chen, Leo Martinez
BACKGROUND Mass tuberculosis screening has been recommended in certain high-risk populations. However, population-based screening interventions have rarely been implemented. Whether mass screening improves health equity is unknown. METHODS We implemented a mass tuberculosis screening intervention among elderly persons (>60 years old) in Lanxi county, China. Standardized questionnaires, physical examinations, and X-rays were administered to all participants. Systematic testing with computed tomography, smear, culture, or Xpert was performed among persons with an abnormal X-ray. We assessed tuberculosis prevalence per 100,000 persons and constructed multivariable regression models among subgroups that were and were not screened. Medical insurance was categorized as participation in either a basic or more comprehensive coverage program. RESULTS In total, 49,339 individuals participated in the screening, 32% of the elderly population in Lanxi. 115 screened persons were diagnosed with tuberculosis (233 cases per 100,000 persons), significantly higher than persons not screened (168 cases among 103,979 person-years; prevalence-to-case notification ratio: 1.44; 95% CI, 1.14-1.83). This increase was largely driven by diagnosis of asymptomatic disease during mass screening (N = 57; 50% of cases). Participants with basic medical insurance were multiple times more likely diagnosed through mass screening compared to passive detection (Adjusted Odds Ratio, 4.52; 95% CI, 1.35-21.28). CONCLUSIONS In a population-based, mass tuberculosis screening intervention encompassing over 30% of the elderly population in rural China, case finding was 44% higher than background detection, driven by diagnosis of asymptomatic tuberculosis. Importantly, mass screening identified tuberculosis in people with limited healthcare options that were less likely to be found through background detection.
{"title":"Mass tuberculosis screening among the elderly: A population-based study in a well-confined rural county in eastern China.","authors":"Zhengfang Hu, Meng Zhou, Xin Jiang, Yaling Feng, Zhicheng Yu, Yuhao Li, Songhua Chen, Qian-Ge Wu, W. Wang, C. Horsburgh, Jr., Yu Zhang, Lina Zhou, Chonggao Hu, Kui Liu, Bin Chen, Leo Martinez","doi":"10.2139/ssrn.4297042","DOIUrl":"https://doi.org/10.2139/ssrn.4297042","url":null,"abstract":"BACKGROUND\u0000Mass tuberculosis screening has been recommended in certain high-risk populations. However, population-based screening interventions have rarely been implemented. Whether mass screening improves health equity is unknown.\u0000\u0000\u0000METHODS\u0000We implemented a mass tuberculosis screening intervention among elderly persons (>60 years old) in Lanxi county, China. Standardized questionnaires, physical examinations, and X-rays were administered to all participants. Systematic testing with computed tomography, smear, culture, or Xpert was performed among persons with an abnormal X-ray. We assessed tuberculosis prevalence per 100,000 persons and constructed multivariable regression models among subgroups that were and were not screened. Medical insurance was categorized as participation in either a basic or more comprehensive coverage program.\u0000\u0000\u0000RESULTS\u0000In total, 49,339 individuals participated in the screening, 32% of the elderly population in Lanxi. 115 screened persons were diagnosed with tuberculosis (233 cases per 100,000 persons), significantly higher than persons not screened (168 cases among 103,979 person-years; prevalence-to-case notification ratio: 1.44; 95% CI, 1.14-1.83). This increase was largely driven by diagnosis of asymptomatic disease during mass screening (N = 57; 50% of cases). Participants with basic medical insurance were multiple times more likely diagnosed through mass screening compared to passive detection (Adjusted Odds Ratio, 4.52; 95% CI, 1.35-21.28).\u0000\u0000\u0000CONCLUSIONS\u0000In a population-based, mass tuberculosis screening intervention encompassing over 30% of the elderly population in rural China, case finding was 44% higher than background detection, driven by diagnosis of asymptomatic tuberculosis. Importantly, mass screening identified tuberculosis in people with limited healthcare options that were less likely to be found through background detection.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80575905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-06-18DOI: 10.1101/2023.06.16.23291449
Stefka Dzieciolowska, H. Charest, Tonya Roy, J. Fafard, S. Carazo, I. Levade, Jean Longtin, Leighanne O. Parkes, Sylvie-Nancy Beaulac, J. Villeneuve, Patrice Savard, Jacques Corbeil, G. De Serres, Y. Longtin
Background: There is a need to understand the duration of infectivity of primary and recurrent COVID-19 and identify predictors of loss of infectivity. Methods: Prospective observational cohort study with serial viral culture, rapid antigen detection test (RADT) and RT-PCR on nasopharyngeal specimens of healthcare workers with COVID-19. The primary outcome was viral culture positivity as indicative of infectivity. Predictors of loss of infectivity were determined using multivariate regression model. The performance of the US CDC criteria (fever resolution, symptom improvement and negative RADT) to predict loss of infectivity was also investigated. Results: 121 participants (91 female [79.3%]; average age, 40 years) were enrolled. Most (n=107, 88.4%) had received [≥]3 SARS-CoV-2 vaccine doses, and 20 (16.5%) had COVID-19 previously. Viral culture positivity decreased from 71.9% (87/121) on day 5 of infection to 18.2% (22/121) on day 10. Participants with recurrent COVID-19 had a lower likelihood of infectivity than those with primary COVID-19 at each follow-up (day 5 OR, 0.14; p<0.001]; day 7 OR, 0.04; p=0.003]) and were all non-infective by day 10 (p=0.02). Independent predictors of infectivity included prior COVID-19 (adjusted OR [aOR] on day 5, 0.005; p=0.003), a RT-PCR Ct value <23 (aOR on day 5, 22.75; p<0.001), but not symptom improvement or RADT result. The CDC criteria would identify 36% (24/67) of all non-infectious individuals on Day 7. However, 17% (5/29) of those meeting all the criteria had a positive viral culture. Conclusions: Infectivity of recurrent COVID-19 is shorter than primary infections. Loss of infectivity algorithms could be optimized.
{"title":"Timing and Predictors of Loss of Infectivity among Healthcare Workers with Primary and Recurrent COVID-19: a Prospective Observational Cohort Study","authors":"Stefka Dzieciolowska, H. Charest, Tonya Roy, J. Fafard, S. Carazo, I. Levade, Jean Longtin, Leighanne O. Parkes, Sylvie-Nancy Beaulac, J. Villeneuve, Patrice Savard, Jacques Corbeil, G. De Serres, Y. Longtin","doi":"10.1101/2023.06.16.23291449","DOIUrl":"https://doi.org/10.1101/2023.06.16.23291449","url":null,"abstract":"Background: There is a need to understand the duration of infectivity of primary and recurrent COVID-19 and identify predictors of loss of infectivity. Methods: Prospective observational cohort study with serial viral culture, rapid antigen detection test (RADT) and RT-PCR on nasopharyngeal specimens of healthcare workers with COVID-19. The primary outcome was viral culture positivity as indicative of infectivity. Predictors of loss of infectivity were determined using multivariate regression model. The performance of the US CDC criteria (fever resolution, symptom improvement and negative RADT) to predict loss of infectivity was also investigated. Results: 121 participants (91 female [79.3%]; average age, 40 years) were enrolled. Most (n=107, 88.4%) had received [≥]3 SARS-CoV-2 vaccine doses, and 20 (16.5%) had COVID-19 previously. Viral culture positivity decreased from 71.9% (87/121) on day 5 of infection to 18.2% (22/121) on day 10. Participants with recurrent COVID-19 had a lower likelihood of infectivity than those with primary COVID-19 at each follow-up (day 5 OR, 0.14; p<0.001]; day 7 OR, 0.04; p=0.003]) and were all non-infective by day 10 (p=0.02). Independent predictors of infectivity included prior COVID-19 (adjusted OR [aOR] on day 5, 0.005; p=0.003), a RT-PCR Ct value <23 (aOR on day 5, 22.75; p<0.001), but not symptom improvement or RADT result. The CDC criteria would identify 36% (24/67) of all non-infectious individuals on Day 7. However, 17% (5/29) of those meeting all the criteria had a positive viral culture. Conclusions: Infectivity of recurrent COVID-19 is shorter than primary infections. Loss of infectivity algorithms could be optimized.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81638501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-03-12DOI: 10.1101/2023.03.10.23286967
A. Naficy, Adrienne Kuxhausen, P. Pirrotta, B. Leav, Jacqueline Miller, Kate Anteyi, J. Danier, Thomas Breuer, A. Mwakingwe-Omari
Background: There is growing consensus that COVID-19 booster vaccines may be coadministered with other age-appropriate vaccines. Adding to the limited available data supporting coadministration, especially with adjuvanted vaccines, could enhance vaccine coverage in adults. Methods: In this phase 3, randomized, open-label study, eligible adults aged [≥]50 years were randomly assigned (1:1) to receive mRNA-1273 (50g) booster vaccination and a first dose of recombinant zoster vaccine (RZV1) 2 weeks apart (Seq group) or concomitantly (Coad group). The second RZV dose (RZV2) was administered 2 months post RZV1 in both groups. Primary objectives were noninferiority of anti-glycoprotein E and anti-Spike protein antibody responses in the Coad group compared to the Seq group. Safety and further immunogenicity assessments were secondary objectives. Results: 273 participants were randomized to the Seq group, 272 to the Coad group. Protocol-specified non-inferiority criteria were met. The adjusted geometric mean concentration ratio (Seq/Coad) was 1.01 (95% confidence interval [CI], 0.89-1.13) for anti-gE antibodies 1-month post-RZV2, and 1.09 (95% CI 0.90-1.32) for anti-Spike antibodies 1-month post-mRNA-1273 booster. No clinically relevant differences were observed in overall frequency, intensity, or duration of adverse events between the 2 study groups. Most solicited adverse events were mild/moderate in intensity, each with median duration [≤]2.5 days. Administration site pain and myalgia were the most frequently reported in both groups. Conclusions: Coadministration of mRNA-1273 booster vaccine with RZV in adults aged [≥]50 years was immunologically noninferior to sequential administration and had a safety and reactogenicity profile consistent with both vaccines administered sequentially (clinicaltrials.gov NCT05047770).
背景:越来越多的共识认为，COVID-19加强疫苗可与其他适龄疫苗共同接种。在现有有限的支持联合接种的数据基础上，特别是与佐剂疫苗联合接种，可以提高成人的疫苗覆盖率。方法:在这项3期随机、开放标签研究中，年龄[≥]50岁的符合条件的成年人被随机分配(1:1)接受mRNA-1273 (50g)加强疫苗接种，并间隔2周(Seq组)或同时(Coad组)接种第一剂重组带状疱疹疫苗(RZV1)。第二剂RZV (RZV2)在两组RZV1后2个月给予。主要目的是与Seq组相比，Coad组的抗糖蛋白E和抗刺突蛋白抗体反应的非劣效性。安全性和进一步的免疫原性评估是次要目标。结果:273名受试者被随机分为Seq组，272名受试者被随机分为Coad组。符合方案规定的非劣效性标准。rzv2后1个月的抗ge抗体校正几何平均浓度比(Seq/Coad)为1.01(95%可信区间[CI]， 0.89-1.13)， mrna -1273增强剂后1个月的抗spike抗体校正几何平均浓度比(Seq/Coad)为1.09 (95% CI 0.90-1.32)。在两个研究组之间，不良事件的总体频率、强度或持续时间没有观察到临床相关的差异。大多数征求的不良事件为轻度/中度强度，每个不良事件的中位持续时间[≤]2.5天。两组患者均以给药部位疼痛和肌痛最为常见。结论:在年龄≥50岁的成人中，mRNA-1273加强疫苗与RZV联合接种在免疫学上不逊于序贯给药，其安全性和反应原性与两种疫苗序贯给药一致(clinicaltrials.gov NCT05047770)。
{"title":"No immunological interference or safety concerns when adjuvanted recombinant zoster vaccine is coadministered with a COVID-19 mRNA-1273 booster vaccine in adults aged 50 years and older: A randomized trial","authors":"A. Naficy, Adrienne Kuxhausen, P. Pirrotta, B. Leav, Jacqueline Miller, Kate Anteyi, J. Danier, Thomas Breuer, A. Mwakingwe-Omari","doi":"10.1101/2023.03.10.23286967","DOIUrl":"https://doi.org/10.1101/2023.03.10.23286967","url":null,"abstract":"Background: There is growing consensus that COVID-19 booster vaccines may be coadministered with other age-appropriate vaccines. Adding to the limited available data supporting coadministration, especially with adjuvanted vaccines, could enhance vaccine coverage in adults. Methods: In this phase 3, randomized, open-label study, eligible adults aged [≥]50 years were randomly assigned (1:1) to receive mRNA-1273 (50g) booster vaccination and a first dose of recombinant zoster vaccine (RZV1) 2 weeks apart (Seq group) or concomitantly (Coad group). The second RZV dose (RZV2) was administered 2 months post RZV1 in both groups. Primary objectives were noninferiority of anti-glycoprotein E and anti-Spike protein antibody responses in the Coad group compared to the Seq group. Safety and further immunogenicity assessments were secondary objectives. Results: 273 participants were randomized to the Seq group, 272 to the Coad group. Protocol-specified non-inferiority criteria were met. The adjusted geometric mean concentration ratio (Seq/Coad) was 1.01 (95% confidence interval [CI], 0.89-1.13) for anti-gE antibodies 1-month post-RZV2, and 1.09 (95% CI 0.90-1.32) for anti-Spike antibodies 1-month post-mRNA-1273 booster. No clinically relevant differences were observed in overall frequency, intensity, or duration of adverse events between the 2 study groups. Most solicited adverse events were mild/moderate in intensity, each with median duration [≤]2.5 days. Administration site pain and myalgia were the most frequently reported in both groups. Conclusions: Coadministration of mRNA-1273 booster vaccine with RZV in adults aged [≥]50 years was immunologically noninferior to sequential administration and had a safety and reactogenicity profile consistent with both vaccines administered sequentially (clinicaltrials.gov NCT05047770).","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87294673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
T. Mohammed, M. Bowe, Alexandria N Plant, M. Perez, Carlos Álvarez, E. Mortensen
BACKGROUND Recent studies suggest that metformin use may be associated with improved infectious disease-related outcomes, whereas other papers suggest potentially worse outcomes in serious bacterial infections. Our purpose was to examine the association of prior outpatient prescription of metformin on 30- and 90-day mortality for older veterans with pre-existing diabetes hospitalized with pneumonia. METHODS We conducted a retrospective cohort study using national Department of Veterans Affairs data of patients ≥65 years with a prior history of diabetes who were hospitalized with pneumonia over a 10-year period (fiscal years 2002-2012.) For our primary analysis, we created a propensity score and matched metformin users to nonusers 1:1. RESULTS We identified 34 759 patients who met the inclusion criteria, 20.3% of whom were prescribed metformin. Unadjusted 30-day mortality was 9.6% for those who received metformin versus 13.9% in nonusers (P < .003), and 90-day mortality was 15.8% for those who received metformin versus 23.0% for nonusers (P < .0001). For the propensity score model, we matched 6899 metformin users to 6899 nonusers. After propensity matching, both 30-day (relative risk [RR]: .86; 95% confidence interval [CI]: .78-.95) and 90-day (RR: .85; 95% CI: .79-.92) mortality was significantly lower for metformin users. CONCLUSIONS Prior receipt of metformin was associated with significantly lower mortality after adjusting for potential confounders. Additional research is needed to examine the safety and potential benefits of metformin use in patients with respiratory infections.
{"title":"Metformin Use Is Associated With Lower Mortality in Veterans With Diabetes Hospitalized With Pneumonia.","authors":"T. Mohammed, M. Bowe, Alexandria N Plant, M. Perez, Carlos Álvarez, E. Mortensen","doi":"10.2139/ssrn.4107159","DOIUrl":"https://doi.org/10.2139/ssrn.4107159","url":null,"abstract":"BACKGROUND\u0000Recent studies suggest that metformin use may be associated with improved infectious disease-related outcomes, whereas other papers suggest potentially worse outcomes in serious bacterial infections. Our purpose was to examine the association of prior outpatient prescription of metformin on 30- and 90-day mortality for older veterans with pre-existing diabetes hospitalized with pneumonia.\u0000\u0000\u0000METHODS\u0000We conducted a retrospective cohort study using national Department of Veterans Affairs data of patients ≥65 years with a prior history of diabetes who were hospitalized with pneumonia over a 10-year period (fiscal years 2002-2012.) For our primary analysis, we created a propensity score and matched metformin users to nonusers 1:1.\u0000\u0000\u0000RESULTS\u0000We identified 34 759 patients who met the inclusion criteria, 20.3% of whom were prescribed metformin. Unadjusted 30-day mortality was 9.6% for those who received metformin versus 13.9% in nonusers (P < .003), and 90-day mortality was 15.8% for those who received metformin versus 23.0% for nonusers (P < .0001). For the propensity score model, we matched 6899 metformin users to 6899 nonusers. After propensity matching, both 30-day (relative risk [RR]: .86; 95% confidence interval [CI]: .78-.95) and 90-day (RR: .85; 95% CI: .79-.92) mortality was significantly lower for metformin users.\u0000\u0000\u0000CONCLUSIONS\u0000Prior receipt of metformin was associated with significantly lower mortality after adjusting for potential confounders. Additional research is needed to examine the safety and potential benefits of metformin use in patients with respiratory infections.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"127 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78706338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Sinha, C. Ponnuraja, N. Gupte, S. Prakash Babu, S. Cox, S. Sarkar, V. Mave, Mandar Paradkar, C. Cintron, S. Govindarajan, A. Kinikar, N. Priya, S. Gaikwad, B. Thangakunam, Arutselvi Devarajan, M. Dhanasekaran, J. Tornheim, Amita Gupta, P. Salgame, D. J. Christopher, H. Kornfeld, V. Viswanathan, J. Ellner, C. Horsburgh, Jr., A. Gupte, C. Padmapriyadarsini, N. Hochberg
BACKGROUND Undernutrition is the leading risk factor for tuberculosis (TB) globally. Its impact on treatment outcomes is poorly defined. METHODS We conducted a prospective cohort analysis of adults with drug-sensitive pulmonary TB at five sites in the Regional Prospective Observational Research on Tuberculosis (RePORT) India consortium (2015-2019). Using multivariable Poisson regression, we assessed independent associations between unfavorable outcomes and nutritional status based on body mass index (BMI) nutritional status at treatment initiation, BMI prior to TB disease, stunting, and stagnant or declining BMI after two months of TB treatment. Unfavorable outcome was defined as a composite of treatment failure, death, or relapse within 6 months of treatment completion. FINDINGS Severe undernutrition (BMI < 16 kg/m2) at treatment initiation and severe undernutrition before the onset of TB disease were both associated with unfavorable outcomes (adjusted incidence rate ratio [aIRR]: 2.05; 95% confidence interval [CI]: 1.42-2.91 and 2.20; 95% CI: 1.16-3.94, respectively). Additionally, lack of BMI increase after treatment initiation was associated with increased unfavorable outcomes (aIRR: 1.81; 95% CI: 1.27-2.61). Severe stunting (height-for-age z-score < -3) was associated with unfavorable outcomes (aIRR: 1.52; 95% CI: 1.00-2.24). Severe undernutrition at treatment initiation and lack of BMI increase during treatment were associated with a four and five-fold higher rate of death, respectively. INTERPRETATIONS Premorbid undernutrition, undernutrition at treatment initiation, lack of BMI increase after intensive therapy, and severe stunting are associated with unfavorable TB treatment outcomes. These data highlight the need for addressing this widely prevalent TB comorbidity. Nutritional assessment should be integrated into standard TB care.
{"title":"Impact of Undernutrition on Tuberculosis Treatment Outcomes in India: A Multicenter Prospective Cohort Analysis.","authors":"P. Sinha, C. Ponnuraja, N. Gupte, S. Prakash Babu, S. Cox, S. Sarkar, V. Mave, Mandar Paradkar, C. Cintron, S. Govindarajan, A. Kinikar, N. Priya, S. Gaikwad, B. Thangakunam, Arutselvi Devarajan, M. Dhanasekaran, J. Tornheim, Amita Gupta, P. Salgame, D. J. Christopher, H. Kornfeld, V. Viswanathan, J. Ellner, C. Horsburgh, Jr., A. Gupte, C. Padmapriyadarsini, N. Hochberg","doi":"10.2139/ssrn.4077891","DOIUrl":"https://doi.org/10.2139/ssrn.4077891","url":null,"abstract":"BACKGROUND\u0000Undernutrition is the leading risk factor for tuberculosis (TB) globally. Its impact on treatment outcomes is poorly defined.\u0000\u0000\u0000METHODS\u0000We conducted a prospective cohort analysis of adults with drug-sensitive pulmonary TB at five sites in the Regional Prospective Observational Research on Tuberculosis (RePORT) India consortium (2015-2019). Using multivariable Poisson regression, we assessed independent associations between unfavorable outcomes and nutritional status based on body mass index (BMI) nutritional status at treatment initiation, BMI prior to TB disease, stunting, and stagnant or declining BMI after two months of TB treatment. Unfavorable outcome was defined as a composite of treatment failure, death, or relapse within 6 months of treatment completion.\u0000\u0000\u0000FINDINGS\u0000Severe undernutrition (BMI < 16 kg/m2) at treatment initiation and severe undernutrition before the onset of TB disease were both associated with unfavorable outcomes (adjusted incidence rate ratio [aIRR]: 2.05; 95% confidence interval [CI]: 1.42-2.91 and 2.20; 95% CI: 1.16-3.94, respectively). Additionally, lack of BMI increase after treatment initiation was associated with increased unfavorable outcomes (aIRR: 1.81; 95% CI: 1.27-2.61). Severe stunting (height-for-age z-score < -3) was associated with unfavorable outcomes (aIRR: 1.52; 95% CI: 1.00-2.24). Severe undernutrition at treatment initiation and lack of BMI increase during treatment were associated with a four and five-fold higher rate of death, respectively.\u0000\u0000\u0000INTERPRETATIONS\u0000Premorbid undernutrition, undernutrition at treatment initiation, lack of BMI increase after intensive therapy, and severe stunting are associated with unfavorable TB treatment outcomes. These data highlight the need for addressing this widely prevalent TB comorbidity. Nutritional assessment should be integrated into standard TB care.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89090477","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-11-22DOI: 10.1101/2022.11.21.22282610
Bridget E. Barber, Azrin N. Abd-Rahman, Rebecca Webster, A. Potter, S. Llewellyn, L. Marquart, Nischal Sahai, Indika Leelasena, G. Birrell, M. Edstein, G. Shanks, D. Wesche, Joerg J. Moehrle, J. McCarthy
Background The long acting 8-aminoquinoline tafenoquine may be a good candidate for mass drug administration if it exhibits sufficient blood stage antimalarial activity at doses low enough to be tolerated by glucose 6-phosphate dehydrogenase (G6PD) deficient individuals. Methods Healthy G6PD-normal adults were inoculated with Plasmodium falciparum 3D7-infected erythrocytes on day 0. Different single oral doses of tafenoquine were administered on day 8. Parasitemia, and concentrations of tafenoquine and the 5,6-orthoquinone metabolite in plasma/whole blood/urine were measured and standard safety assessments performed. Curative artemether-lumefantrine therapy was administered if parasite regrowth occurred, or on day 48+/-2. Outcomes were parasite clearance kinetics, pharmacokinetic and pharmacokinetic/pharmacodynamic (PK/PD) parameters from modelling, and dose simulations in a theoretical endemic population. Results Twelve participants were inoculated and administered 200 mg (n=3), 300 mg (n=4), 400 mg (n=2), or 600 mg (n=3) tafenoquine. The parasite clearance half-life with 400 mg or 600 mg (5.4 h and 4.2 h respectively) was faster than with 200 mg or 300 mg (11.8 h and 9.6 h respectively). Parasite regrowth occurred after dosing with 200 mg (3/3 participants) and 300 mg (3/4 participants), but not after 400 mg or 600 mg. Simulations using the PK/PD model predicted that 460 mg and 540 mg would clear parasitaemia by a factor of 10^6 and 10^9, respectively, in a 60 kg adult. Conclusions Although a single dose or tafenoquine exhibits potent P. falciparum blood stage antimalarial activity, the estimated doses to effectively clear asexual parasitemia will require prior screening to exclude G6PD deficiency.
{"title":"Characterizing the Blood-Stage Antimalarial Activity of Tafenoquine in Healthy Volunteers Experimentally Infected With Plasmodium falciparum","authors":"Bridget E. Barber, Azrin N. Abd-Rahman, Rebecca Webster, A. Potter, S. Llewellyn, L. Marquart, Nischal Sahai, Indika Leelasena, G. Birrell, M. Edstein, G. Shanks, D. Wesche, Joerg J. Moehrle, J. McCarthy","doi":"10.1101/2022.11.21.22282610","DOIUrl":"https://doi.org/10.1101/2022.11.21.22282610","url":null,"abstract":"Background The long acting 8-aminoquinoline tafenoquine may be a good candidate for mass drug administration if it exhibits sufficient blood stage antimalarial activity at doses low enough to be tolerated by glucose 6-phosphate dehydrogenase (G6PD) deficient individuals. Methods Healthy G6PD-normal adults were inoculated with Plasmodium falciparum 3D7-infected erythrocytes on day 0. Different single oral doses of tafenoquine were administered on day 8. Parasitemia, and concentrations of tafenoquine and the 5,6-orthoquinone metabolite in plasma/whole blood/urine were measured and standard safety assessments performed. Curative artemether-lumefantrine therapy was administered if parasite regrowth occurred, or on day 48+/-2. Outcomes were parasite clearance kinetics, pharmacokinetic and pharmacokinetic/pharmacodynamic (PK/PD) parameters from modelling, and dose simulations in a theoretical endemic population. Results Twelve participants were inoculated and administered 200 mg (n=3), 300 mg (n=4), 400 mg (n=2), or 600 mg (n=3) tafenoquine. The parasite clearance half-life with 400 mg or 600 mg (5.4 h and 4.2 h respectively) was faster than with 200 mg or 300 mg (11.8 h and 9.6 h respectively). Parasite regrowth occurred after dosing with 200 mg (3/3 participants) and 300 mg (3/4 participants), but not after 400 mg or 600 mg. Simulations using the PK/PD model predicted that 460 mg and 540 mg would clear parasitaemia by a factor of 10^6 and 10^9, respectively, in a 60 kg adult. Conclusions Although a single dose or tafenoquine exhibits potent P. falciparum blood stage antimalarial activity, the estimated doses to effectively clear asexual parasitemia will require prior screening to exclude G6PD deficiency.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"2 1","pages":"1919 - 1927"},"PeriodicalIF":0.0,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87915958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Primary Care Guidance for Persons With Human Immunodeficiency Virus: 2020 Update by the HIV Medicine Association of the Infectious Diseases Society of America.","authors":"","doi":"10.1093/cid/ciac474","DOIUrl":"https://doi.org/10.1093/cid/ciac474","url":null,"abstract":"","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91267602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-05DOI: 10.1101/2022.10.05.22280702
A. Price, B. Flannery, K. Talbot, Carlos G. Grijalva, K. Wernli, H. Phillips, A. Monto, E. Martin, E. Belongia, H. McLean, M. Gaglani, M. Mutnal, K. M. Geffel, M. Nowalk, S. Tartof, A. Florea, C. McLean, S. Kim, M. Patel, J. Chung
Background. In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness for the first time since the beginning of the COVID-19 pandemic. We estimated influenza vaccine effectiveness against lab-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. Methods. Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged [≥]6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and SARS-CoV-2 vaccination, participants who tested positive for SARS-CoV-2 were excluded from vaccine effectiveness estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity and general health status. Results. Among 6,260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1,948 SARS-CoV-2 positive patients, 4,312 patients were included in analyses of influenza VE; 2,463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95%CI, 20-49%) overall; 40% (95%CI, 24-53%) for those aged 6 months-49 years; and 10% (95%CI, -60-49%) for those aged [≥]50 years. Conclusion. Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons, with no measurable protection among older adults.
{"title":"Influenza Vaccine Effectiveness Against Influenza A(H3N2)-Related Illness in the United States During the 2021-2022 Influenza Season","authors":"A. Price, B. Flannery, K. Talbot, Carlos G. Grijalva, K. Wernli, H. Phillips, A. Monto, E. Martin, E. Belongia, H. McLean, M. Gaglani, M. Mutnal, K. M. Geffel, M. Nowalk, S. Tartof, A. Florea, C. McLean, S. Kim, M. Patel, J. Chung","doi":"10.1101/2022.10.05.22280702","DOIUrl":"https://doi.org/10.1101/2022.10.05.22280702","url":null,"abstract":"Background. In the United States, influenza activity during the 2021-2022 season was modest and sufficient enough to estimate influenza vaccine effectiveness for the first time since the beginning of the COVID-19 pandemic. We estimated influenza vaccine effectiveness against lab-confirmed outpatient acute illness caused by predominant A(H3N2) viruses. Methods. Between October 2021 and April 2022, research staff across 7 sites enrolled patients aged [≥]6 months seeking outpatient care for acute respiratory illness with cough. Using a test-negative design, we assessed VE against influenza A(H3N2). Due to strong correlation between influenza and SARS-CoV-2 vaccination, participants who tested positive for SARS-CoV-2 were excluded from vaccine effectiveness estimations. Estimates were adjusted for site, age, month of illness, race/ethnicity and general health status. Results. Among 6,260 participants, 468 (7%) tested positive for influenza only, including 440 (94%) for A(H3N2). All 206 sequenced A(H3N2) viruses were characterized as belonging to genetic group 3C.2a1b subclade 2a.2, which has antigenic differences from the 2021-2022 season A(H3N2) vaccine component that belongs to clade 3C.2a1b subclade 2a.1. After excluding 1,948 SARS-CoV-2 positive patients, 4,312 patients were included in analyses of influenza VE; 2,463 (57%) were vaccinated against influenza. Effectiveness against A(H3N2) for all ages was 36% (95%CI, 20-49%) overall; 40% (95%CI, 24-53%) for those aged 6 months-49 years; and 10% (95%CI, -60-49%) for those aged [≥]50 years. Conclusion. Influenza vaccination in 2021-2022 provided protection against influenza A(H3N2)-related outpatient visits among young persons, with no measurable protection among older adults.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"36 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87665825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-20DOI: 10.1101/2022.09.19.22280087
Maria Ubals, E. Tarín-Vicente, Xènia Oller, Adrià Mendoza, A. Alemany, Á. Hernández-Rodríguez, C. Casañ, Á. Rivero, P. Coll, José Miguel Cabrera, M. Vall, M. Agud-Dios, Elena Gil-Cruz, A. París de León, A. Ramírez, M. D. Folgueira, María de los Ángeles Meléndez, Vira Buhiichyk, C. Galván-Casas, R. Paredes, N. Prat, M. S. Sala Farré, J. M. Bonet-Simó, P. Ortiz-Romero, B. Clotet, P. Cardona, I. Blanco, M. Marks, Clara Suñer, O. Mitjà
We evaluated the accuracy of patient-collected skin lesions, pharyngeal, and rectal swabs amongst 50 individuals enrolled in a study of monkeypox viral dynamics. We found that the performance of self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable strategy for diagnosing monkeypox.
{"title":"Evaluating the accuracy of self-collected swabs for the diagnosis of monkeypox","authors":"Maria Ubals, E. Tarín-Vicente, Xènia Oller, Adrià Mendoza, A. Alemany, Á. Hernández-Rodríguez, C. Casañ, Á. Rivero, P. Coll, José Miguel Cabrera, M. Vall, M. Agud-Dios, Elena Gil-Cruz, A. París de León, A. Ramírez, M. D. Folgueira, María de los Ángeles Meléndez, Vira Buhiichyk, C. Galván-Casas, R. Paredes, N. Prat, M. S. Sala Farré, J. M. Bonet-Simó, P. Ortiz-Romero, B. Clotet, P. Cardona, I. Blanco, M. Marks, Clara Suñer, O. Mitjà","doi":"10.1101/2022.09.19.22280087","DOIUrl":"https://doi.org/10.1101/2022.09.19.22280087","url":null,"abstract":"We evaluated the accuracy of patient-collected skin lesions, pharyngeal, and rectal swabs amongst 50 individuals enrolled in a study of monkeypox viral dynamics. We found that the performance of self-collected samples was similar to that of physician-collected samples, suggesting that self-sampling is a reliable strategy for diagnosing monkeypox.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"21 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87544353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-08-29DOI: 10.1093/cid/ciac689/6678599
J. Burry, C. P. Casas, N. Ford
Cryptococcal meningitis accounts for one in five AIDS-related deaths globally. WHO guidelines strongly recommend a single high-dose of liposomal amphotericin B as part of preferred treatment, but this drug remains unaffordable in most low- and middle-income countries. A proactive approach is needed from manufacturers and other stakeholders to improve access.
{"title":"Access to medicines for treating people with cryptococcal meningitis","authors":"J. Burry, C. P. Casas, N. Ford","doi":"10.1093/cid/ciac689/6678599","DOIUrl":"https://doi.org/10.1093/cid/ciac689/6678599","url":null,"abstract":"Cryptococcal meningitis accounts for one in five AIDS-related deaths globally. WHO guidelines strongly recommend a single high-dose of liposomal amphotericin B as part of preferred treatment, but this drug remains unaffordable in most low- and middle-income countries. A proactive approach is needed from manufacturers and other stakeholders to improve access.","PeriodicalId":10421,"journal":{"name":"Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America","volume":"16 1","pages":"e773 - e775"},"PeriodicalIF":0.0,"publicationDate":"2022-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81138437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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