Pub Date : 2024-09-14DOI: 10.1101/2024.09.13.24313632
Xuan Wang, Ankit Pahwa, Mary T. Bausch-Jurken, Anushri Chitkara, Pawana Sharma, Mia Malmenas, Sonam Vats, Michael Gordon Whitfield, Kira Zhi Hua Lai, Priyadarsini Dasari, Ritu Gupta, Maria Nassim, Nicolas Van de Velde, Nathan Green, Ekkehard Beck
Introduction: This systematic literature review and pairwise meta-analysis evaluated the comparative effectiveness of mRNA-1273 versus BNT162b in patients with at least one underlying medical condition at high risk for severe COVID-19. Methods: MEDLINE, Embase, and Cochrane databases were searched for relevant articles from January 1, 2019 to February 9, 2024. Studies reporting effectiveness data from at least two doses of mRNA-1273 and BNT162b2 vaccination in adults with medical conditions at high risk of developing severe COVID-19 according to the US Centers for Disease Control and Prevention were included. Outcomes of interest were SARS-CoV-2 infection (overall, symptomatic, and severe), hospitalization due to COVID-19, and death due to COVID-19. Risk ratios (RRs) were calculated with random effects models. Subgroup analyses by specific medical conditions, number of vaccinations, age, and SARS-CoV-2 variant were conducted. Heterogeneity between studies was estimated with chi-square testing. The certainty of evidence was assessed using the Grading of Recommendations, Assessments, Development, and Evaluations framework. Results: Sixty-five observational studies capturing the original/ancestral-containing primary series to Omicron-containing bivalent original-BA4-5 vaccinations were included in the meta-analysis. mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.79-0.92]; I2=92.5%), symptomatic SARS-CoV-2 infection (RR, 0.75 [95% CI, 0.65-0.86]; I2=62.3%), severe SARS-CoV-2 infection (RR, 0.83 [95% CI, 0.78-0.89]; I2=38.0%), hospitalization due to COVID-19 (RR, 0.88 [95% CI, 0.82-0.94]; I2=38.7%), and death due to COVID-19 (RR, 0.84 [95% CI, 0.76-0.93]; I2=1.3%) than BNT162b2. Findings were generally consistent across subgroups. Evidence certainty was low or very low because sufficiently powered randomized controlled trials are impractical in this heterogeneous population. Conclusion: Meta-analysis of 65 observational studies showed that vaccination with mRNA-1273 was associated with a significantly lower risk of SARS-CoV-2 infection and COVID-19-related hospitalization and death than BNT162b2 in patients with medical conditions at high risk of severe COVID-19.
{"title":"Comparative Effectiveness of the mRNA-1273 and BNT162b2 COVID-19 Vaccines Among Adults With Underlying Medical Conditions: A Systematic Literature Review and Pairwise Meta-Analysis Using GRADE","authors":"Xuan Wang, Ankit Pahwa, Mary T. Bausch-Jurken, Anushri Chitkara, Pawana Sharma, Mia Malmenas, Sonam Vats, Michael Gordon Whitfield, Kira Zhi Hua Lai, Priyadarsini Dasari, Ritu Gupta, Maria Nassim, Nicolas Van de Velde, Nathan Green, Ekkehard Beck","doi":"10.1101/2024.09.13.24313632","DOIUrl":"https://doi.org/10.1101/2024.09.13.24313632","url":null,"abstract":"Introduction: This systematic literature review and pairwise meta-analysis evaluated the comparative effectiveness of mRNA-1273 versus BNT162b in patients with at least one underlying medical condition at high risk for severe COVID-19. Methods: MEDLINE, Embase, and Cochrane databases were searched for relevant articles from January 1, 2019 to February 9, 2024. Studies reporting effectiveness data from at least two doses of mRNA-1273 and BNT162b2 vaccination in adults with medical conditions at high risk of developing severe COVID-19 according to the US Centers for Disease Control and Prevention were included. Outcomes of interest were SARS-CoV-2 infection (overall, symptomatic, and severe), hospitalization due to COVID-19, and death due to COVID-19. Risk ratios (RRs) were calculated with random effects models. Subgroup analyses by specific medical conditions, number of vaccinations, age, and SARS-CoV-2 variant were conducted. Heterogeneity between studies was estimated with chi-square testing. The certainty of evidence was assessed using the Grading of Recommendations, Assessments, Development, and Evaluations framework. Results: Sixty-five observational studies capturing the original/ancestral-containing primary series to Omicron-containing bivalent original-BA4-5 vaccinations were included in the meta-analysis. mRNA-1273 was associated with significantly lower risk of SARS-CoV-2 infection (RR, 0.85 [95% CI, 0.79-0.92]; I2=92.5%), symptomatic SARS-CoV-2 infection (RR, 0.75 [95% CI, 0.65-0.86]; I2=62.3%), severe SARS-CoV-2 infection (RR, 0.83 [95% CI, 0.78-0.89]; I2=38.0%), hospitalization due to COVID-19 (RR, 0.88 [95% CI, 0.82-0.94]; I2=38.7%), and death due to COVID-19 (RR, 0.84 [95% CI, 0.76-0.93]; I2=1.3%) than BNT162b2. Findings were generally consistent across subgroups. Evidence certainty was low or very low because sufficiently powered randomized controlled trials are impractical in this heterogeneous population. Conclusion: Meta-analysis of 65 observational studies showed that vaccination with mRNA-1273 was associated with a significantly lower risk of SARS-CoV-2 infection and COVID-19-related hospitalization and death than BNT162b2 in patients with medical conditions at high risk of severe COVID-19.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269790","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 : 2024-09-14DOI: 10.1101/2024.09.13.24313549
Lorin Adams, Phoebe Stevenson-Leggett, Jia Le Lee, James Bazire, Giulia Dowgier, Agnieszka Hobbs, Chloe Roustan, Annabel Borg, Christine Carr, Silvia Innocentin, Louise MC Webb, Callie Smith, Philip Bawumia, Nicola Lewis, Nicola O'Reilly, Svend Kjaer, Michelle A Linterman, Ruth Harvey, Mary Y Wu, Edward J Carr
Influenza remains a significant threat to human and animal health. Assessing serological protection against influenza has relied upon haemagglutinin inhibition assays, which are used to gauge existing immune landscapes, seasonal vaccine decisions and in systems vaccinology studies. Here, we adapt our high-throughput live virus microneutralisation assay for SARS-CoV-2, benchmark against haemagglutinin inhibition assays, and report serological vaccine responsiveness in a cohort of older (>65yo) community dwelling adults (n=73), after the adjuvanted 2021-22 Northern Hemisphere quadrivalent vaccine. We performed both assays against all four viruses represented in the vaccine (A/Cambodia/H3N2/2020, A/H1pdm/Victoria/2570/2019, B/Yamagata/Phuket/2013, BVIC/Washington/02/2019), using sera drawn on days 0 [range: d-28 to d0], 7 [d6-10] and 182 [d161-196] with respect to vaccination. We found population-level concordance between the two assays (Spearman's correlation coefficient range 0.48-0.88; all P less than or equal to 1.4 x 10-5). The improved granularity of microneutralisation was better able to estimate fold-changes of responses, and quantify the inhibitory effect of pre-existing antibody. Our high-throughput method offers an alternative approach to assess influenza-specific serological responses with improved resolution.
{"title":"Improved resolution of influenza vaccination responses with high-throughput live virus microneutralisation","authors":"Lorin Adams, Phoebe Stevenson-Leggett, Jia Le Lee, James Bazire, Giulia Dowgier, Agnieszka Hobbs, Chloe Roustan, Annabel Borg, Christine Carr, Silvia Innocentin, Louise MC Webb, Callie Smith, Philip Bawumia, Nicola Lewis, Nicola O'Reilly, Svend Kjaer, Michelle A Linterman, Ruth Harvey, Mary Y Wu, Edward J Carr","doi":"10.1101/2024.09.13.24313549","DOIUrl":"https://doi.org/10.1101/2024.09.13.24313549","url":null,"abstract":"Influenza remains a significant threat to human and animal health. Assessing serological protection against influenza has relied upon haemagglutinin inhibition assays, which are used to gauge existing immune landscapes, seasonal vaccine decisions and in systems vaccinology studies. Here, we adapt our high-throughput live virus microneutralisation assay for SARS-CoV-2, benchmark against haemagglutinin inhibition assays, and report serological vaccine responsiveness in a cohort of older (>65yo) community dwelling adults (n=73), after the adjuvanted 2021-22 Northern Hemisphere quadrivalent vaccine. We performed both assays against all four viruses represented in the vaccine (A/Cambodia/H3N2/2020, A/H1pdm/Victoria/2570/2019, B/Yamagata/Phuket/2013, BVIC/Washington/02/2019), using sera drawn on days 0 [range: d-28 to d0], 7 [d6-10] and 182 [d161-196] with respect to vaccination. We found population-level concordance between the two assays (Spearman's correlation coefficient range 0.48-0.88; all P less than or equal to 1.4 x 10-5). The improved granularity of microneutralisation was better able to estimate fold-changes of responses, and quantify the inhibitory effect of pre-existing antibody. Our high-throughput method offers an alternative approach to assess influenza-specific serological responses with improved resolution.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269785","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 : 2024-09-13DOI: 10.1101/2024.09.11.24313306
Sheila F Lumley, Chris Kent, Daisy Jennings, Haiting Chai, George Airey, Elizabeth Waddilove, Maion Delphin, Amy Trebes, Anna McNaughton, Khadija Said Mohammed, Sam Wilkinson, Yanxia Wu, George MacIntyre-Cockett, Beatrice Kimono, Moses Kwizera, Kevin Ojambo, Tongai Maponga, Catherine de Lara, Jacqueline Martin, James Campbell, Marije Van Schalkwyk, Dominique Goedhals, Robert Newton, Eleanor Barnes, Nicholas J Loman, Paolo Piazza, Joshua Quick, M Azim Ansari, Philippa C Matthews
Hepatitis B virus (HBV) whole genome sequencing (WGS) is currently limited as the DNA viral loads (VL) of many clinical samples are below the threshold required to generate full genomes using current sequencing methods. We developed two pan-genotypic viral enrichment methods, using probe-based capture and tiled amplicon PCR (HEP-TILE) for HBV WGS. We demonstrate using mock samples that both enrichment methods are pan-genotypic (genotypes A-J). Using clinical samples, we demonstrate that HEP-TILE amplification successfully amplifies full genomes at the lowest HBV VL tested (30 IU/ml), and the PCR products can be sequenced using both Nanopore and Illumina platforms. Probe-based capture with Illumina sequencing required VL >300,000 IU/ml to generate full length HBV genomes. The capture-Illumina and HEP-TILE-Nanopore pipelines had consensus sequencing accuracy of 100% in mock samples with known DNA sequences. Together, these protocols will facilitate the generation of HBV sequence data, enabling a more accurate and representative picture of HBV molecular epidemiology, cast light on persistence and pathogenesis, and enhance understanding of the outcomes of infection and its treatment.
{"title":"Whole genome sequencing of hepatitis B virus (HBV) using tiled amplicon (HEP-TILE) and probe-based enrichment on Illumina and Nanopore platforms.","authors":"Sheila F Lumley, Chris Kent, Daisy Jennings, Haiting Chai, George Airey, Elizabeth Waddilove, Maion Delphin, Amy Trebes, Anna McNaughton, Khadija Said Mohammed, Sam Wilkinson, Yanxia Wu, George MacIntyre-Cockett, Beatrice Kimono, Moses Kwizera, Kevin Ojambo, Tongai Maponga, Catherine de Lara, Jacqueline Martin, James Campbell, Marije Van Schalkwyk, Dominique Goedhals, Robert Newton, Eleanor Barnes, Nicholas J Loman, Paolo Piazza, Joshua Quick, M Azim Ansari, Philippa C Matthews","doi":"10.1101/2024.09.11.24313306","DOIUrl":"https://doi.org/10.1101/2024.09.11.24313306","url":null,"abstract":"Hepatitis B virus (HBV) whole genome sequencing (WGS) is currently limited as the DNA viral loads (VL) of many clinical samples are below the threshold required to generate full genomes using current sequencing methods. We developed two pan-genotypic viral enrichment methods, using probe-based capture and tiled amplicon PCR (HEP-TILE) for HBV WGS. We demonstrate using mock samples that both enrichment methods are pan-genotypic (genotypes A-J). Using clinical samples, we demonstrate that HEP-TILE amplification successfully amplifies full genomes at the lowest HBV VL tested (30 IU/ml), and the PCR products can be sequenced using both Nanopore and Illumina platforms. Probe-based capture with Illumina sequencing required VL >300,000 IU/ml to generate full length HBV genomes. The capture-Illumina and HEP-TILE-Nanopore pipelines had consensus sequencing accuracy of 100% in mock samples with known DNA sequences. Together, these protocols will facilitate the generation of HBV sequence data, enabling a more accurate and representative picture of HBV molecular epidemiology, cast light on persistence and pathogenesis, and enhance understanding of the outcomes of infection and its treatment.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265735","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 : 2024-09-13DOI: 10.1101/2024.09.11.24313489
John Huddleston, Trevor Bedford
For the last decade, evolutionary forecasting models have influenced seasonal influenza vaccine design. These models attempt to predict which genetic variants circulating at the time of vaccine strain selection will be dominant 12 months later in the influenza season targeted by vaccination campaign. Forecasting models depend on hemagglutinin (HA) sequences from the WHO's Global Influenza Surveillance and Response System to identify currently circulating groups of related strains (clades) and estimate clade fitness for forecasts. However, the average lag between collection of a clinical sample and the submission of its sequence to the Global Initiative on Sharing All Influenza Data (GISAID) EpiFlu database is ~3 months. Submission lags complicate the already difficult 12-month forecasting problem by reducing understanding of current clade frequencies at the time of forecasting. These constraints of a 12-month forecast horizon and 3-month average submission lags create an upper bound on the accuracy of any long-term forecasting model. The global response to the SARS-CoV-2 pandemic revealed that modern vaccine technology like mRNA vaccines can reduce how far we need to forecast into the future to 6 months or less and that expanded support for sequencing can reduce submission lags to GISAID to 1 month on average. To determine whether these recent advances could also improve long-term forecasts for seasonal influenza, we quantified the effects of reducing forecast horizons and submission lags on the accuracy of forecasts for A/H3N2 populations. We found that reducing forecast horizons from 12 months to 6 or 3 months reduced average absolute forecasting errors to 25% and 50% of the 12-month average, respectively. Reducing submission lags provided little improvement to forecasting accuracy but decreased the uncertainty in current clade frequencies by 50%. These results show the potential to substantially improve the accuracy of existing influenza forecasting models by modernizing influenza vaccine development and increasing global sequencing capacity.
{"title":"Timely vaccine strain selection and genomic surveillance improves evolutionary forecast accuracy of seasonal influenza A/H3N2","authors":"John Huddleston, Trevor Bedford","doi":"10.1101/2024.09.11.24313489","DOIUrl":"https://doi.org/10.1101/2024.09.11.24313489","url":null,"abstract":"For the last decade, evolutionary forecasting models have influenced seasonal influenza vaccine design. These models attempt to predict which genetic variants circulating at the time of vaccine strain selection will be dominant 12 months later in the influenza season targeted by vaccination campaign. Forecasting models depend on hemagglutinin (HA) sequences from the WHO's Global Influenza Surveillance and Response System to identify currently circulating groups of related strains (clades) and estimate clade fitness for forecasts. However, the average lag between collection of a clinical sample and the submission of its sequence to the Global Initiative on Sharing All Influenza Data (GISAID) EpiFlu database is ~3 months. Submission lags complicate the already difficult 12-month forecasting problem by reducing understanding of current clade frequencies at the time of forecasting. These constraints of a 12-month forecast horizon and 3-month average submission lags create an upper bound on the accuracy of any long-term forecasting model. The global response to the SARS-CoV-2 pandemic revealed that modern vaccine technology like mRNA vaccines can reduce how far we need to forecast into the future to 6 months or less and that expanded support for sequencing can reduce submission lags to GISAID to 1 month on average. To determine whether these recent advances could also improve long-term forecasts for seasonal influenza, we quantified the effects of reducing forecast horizons and submission lags on the accuracy of forecasts for A/H3N2 populations. We found that reducing forecast horizons from 12 months to 6 or 3 months reduced average absolute forecasting errors to 25% and 50% of the 12-month average, respectively. Reducing submission lags provided little improvement to forecasting accuracy but decreased the uncertainty in current clade frequencies by 50%. These results show the potential to substantially improve the accuracy of existing influenza forecasting models by modernizing influenza vaccine development and increasing global sequencing capacity.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269788","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 : 2024-09-13DOI: 10.1101/2024.09.12.24313559
Roberto Pineda-Reyes, Miguel M Cabada, Bolor Bold, Maria Luisa Morales, Jan Hattendorf, Paola Vergaray, Ruben Bascope, Jakob Zinsstag
Peru has the highest incidence of human cystic echinococcosis (CE) in South America and most cases are reported in the Central and Southern Peruvian Andes, including the Cusco region. We reviewed medical records of patients with CE admitted between 2010-2019 to a level 2 Hospital in Sicuani, to collect data on the surgical management and disease recurrence in the Canchis province of Cusco. Records of 115 patients were analyzed in detail. The median age was 25 years (IQR, 16-46) and 60% were female. Most patients (68.7%) presented with a single liver cyst. The Gharbi classification was used in 75/107 (70.1%) patients with an ultrasound and 91/142 cysts (64.8%). Thirty one (34.1%) were classified as Gharbi I, 33 (36.3%) Gharbi II, 21 (23.1%) Gharbi III, and 6 (6.6%) Gharbi IV. Pre-surgical complications were reported in 41.7%. One hundred two patients underwent surgery. In 46.1%, one cyst spillage prevention measure was documented, 5.9% had two, and one had the three recommended measures. Post-surgical cyst recurrence was reported in 16.5% at a median 32.3 months (IQR, 3.9-46.6) and readmissions in 12.7%. In the multivariable analysis, having ≥3 cysts (OR 9.5, 95% CI 1.3-85.5), having two pre-surgical complications (OR 12.6, 95% CI 1.8-125.6), and receiving pre-surgical albendazole (OR 5.2, 95% CI 1.3-23.9) were associated with cyst recurrence. Advanced and complicated CE disease and post-surgical recurrence were common in Sicuani. Standardization of ultrasound staging-guided clinical management along with surgical spillage prevention measures could effectively decrease the disease burden linked to clinical care, improving outcomes and decreasing costs.
秘鲁是南美洲人类囊性棘球蚴病（CE）发病率最高的国家，大多数病例都发生在秘鲁安第斯山脉中部和南部，包括库斯科地区。我们查阅了西瓜尼一家二级医院 2010-2019 年间收治的 CE 患者的病历，以收集库斯科坎奇斯省的手术治疗和疾病复发数据。对 115 名患者的病历进行了详细分析。中位年龄为 25 岁（IQR，16-46 岁），60% 为女性。大多数患者（68.7%）只有一个肝囊肿。75/107（70.1%）例患者接受了超声检查，91/142（64.8%）例囊肿采用了加尔比分类法。31例（34.1%）被归为加尔比I型，33例（36.3%）为加尔比II型，21例（23.1%）为加尔比III型，6例（6.6%）为加尔比IV型。据报告，41.7%的患者出现了手术前并发症。122 名患者接受了手术治疗。46.1%的患者采取了一项预防囊肿溢出的措施，5.9%的患者采取了两项措施，还有一名患者采取了三项建议措施。16.5%的患者在手术后中位 32.3 个月（IQR，3.9-46.6）出现囊肿复发，12.7%的患者再次入院。在多变量分析中，囊肿≥3个（OR 9.5，95% CI 1.3-85.5）、术前有两种并发症（OR 12.6，95% CI 1.8-125.6）和术前接受阿苯达唑治疗（OR 5.2，95% CI 1.3-23.9）与囊肿复发有关。晚期和复杂的 CE 疾病以及手术后复发在 Sicuani 很常见。超声分期指导下的临床管理标准化以及手术溢液预防措施可有效降低与临床护理相关的疾病负担，改善预后并降低成本。
{"title":"Clinical management, epidemiology, and recurrence of human cystic echinococcosis in a secondary care level hospital in an endemic area of the Andes in Sicuani, Cusco, Peru","authors":"Roberto Pineda-Reyes, Miguel M Cabada, Bolor Bold, Maria Luisa Morales, Jan Hattendorf, Paola Vergaray, Ruben Bascope, Jakob Zinsstag","doi":"10.1101/2024.09.12.24313559","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313559","url":null,"abstract":"Peru has the highest incidence of human cystic echinococcosis (CE) in South America and most cases are reported in the Central and Southern Peruvian Andes, including the Cusco region. We reviewed medical records of patients with CE admitted between 2010-2019 to a level 2 Hospital in Sicuani, to collect data on the surgical management and disease recurrence in the Canchis province of Cusco. Records of 115 patients were analyzed in detail. The median age was 25 years (IQR, 16-46) and 60% were female. Most patients (68.7%) presented with a single liver cyst. The Gharbi classification was used in 75/107 (70.1%) patients with an ultrasound and 91/142 cysts (64.8%). Thirty one (34.1%) were classified as Gharbi I, 33 (36.3%) Gharbi II, 21 (23.1%) Gharbi III, and 6 (6.6%) Gharbi IV. Pre-surgical complications were reported in 41.7%. One hundred two patients underwent surgery. In 46.1%, one cyst spillage prevention measure was documented, 5.9% had two, and one had the three recommended measures. Post-surgical cyst recurrence was reported in 16.5% at a median 32.3 months (IQR, 3.9-46.6) and readmissions in 12.7%. In the multivariable analysis, having ≥3 cysts (OR 9.5, 95% CI 1.3-85.5), having two pre-surgical complications (OR 12.6, 95% CI 1.8-125.6), and receiving pre-surgical albendazole (OR 5.2, 95% CI 1.3-23.9) were associated with cyst recurrence. Advanced and complicated CE disease and post-surgical recurrence were common in Sicuani. Standardization of ultrasound staging-guided clinical management along with surgical spillage prevention measures could effectively decrease the disease burden linked to clinical care, improving outcomes and decreasing costs.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265733","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 : 2024-09-13DOI: 10.1101/2024.09.11.24313508
Leo A Featherstone, Danielle J. Ingle, Wytamma Wirth, Sebastian Duchene
Phylodynamic analyses enable the inference of epidemiological parameters from pathogen genome sequences for enhanced genomic surveillance in public health. Pathogen genome sequences and their associated sampling times are the essential data in every analysis. However, sampling times are usually associated with hospitalisation or testing dates and can sometimes be used to identify individual patients, posing a threat to patient confidentiality. To lower this risk, sampling times are often given with reduced date-resolution to the month or year, which can potentially bias inference of epidemiological parameters. Here, we characterise the extent to which reduced date-resolution biases phylodynamic analyses across a diverse range of empirical and simulated datasets. We develop a practical guideline on when date-rounding biases phylodynamic inference and we show that this bias is both unpredictable in its direction and compounds with decreasing date-resolution, higher substitution rates, and shorter sampling intervals. We conclude by discussing future solutions that prioritise patient confidentiality and propose a method for safer sharing of sampling dates by translating them uniformly by a random number.
{"title":"How does date-rounding affect phylodynamic inference for public health?","authors":"Leo A Featherstone, Danielle J. Ingle, Wytamma Wirth, Sebastian Duchene","doi":"10.1101/2024.09.11.24313508","DOIUrl":"https://doi.org/10.1101/2024.09.11.24313508","url":null,"abstract":"Phylodynamic analyses enable the inference of epidemiological parameters from pathogen genome sequences for enhanced genomic surveillance in public health. Pathogen genome sequences and their associated sampling times are the essential data in every analysis. However, sampling times are usually associated with hospitalisation or testing dates and can sometimes be used to identify individual patients, posing a threat to patient confidentiality. To lower this risk, sampling times are often given with reduced date-resolution to the month or year, which can potentially bias inference of epidemiological parameters. Here, we characterise the extent to which reduced date-resolution biases phylodynamic analyses across a diverse range of empirical and simulated datasets. We develop a practical guideline on when date-rounding biases phylodynamic inference and we show that this bias is both unpredictable in its direction and compounds with decreasing date-resolution, higher substitution rates, and shorter sampling intervals. We conclude by discussing future solutions that prioritise patient confidentiality and propose a method for safer sharing of sampling dates by translating them uniformly by a random number.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265736","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 : 2024-09-13DOI: 10.1101/2024.09.13.24313492
Sandrena Ruth Frischer, Eloise S Ockenden, Fabian Reitzug, Michael Parker, Goylette F Chami
Background: There is a lack of synthesized evidence on how best to support care continuity for neglected tropical diseases (NTDs) in sub-Saharan Africa (SSA). Methods: To identify all SSA NTD care pathways, we conducted a systematic search of six scientific databases from inception to 18 February 2023. All studies were required to include care pathways for NTDs, defined at minimum as having both NTD diagnosis and treatment or referral to treatment for care continuity. Using an iterative approach to establish an understanding of care pathways relevant for NTDs, concept development drew from data extraction of variables relating to study characteristics; approaches to diagnosis, treatment, and referrals as pathway components; barriers to care and strategies for their resolution; and ethical challenges. Findings: Searches returned 2178 studies where after de-duplication and eligibility screening, 164 were systematically reviewed. Medical referrals were used to support care continuity in 62.2% (102/164) of studies, and community health workers played roles in patient care in 22.6% (37/164) of studies. Only 6.7% (11/164) of studies explicitly mapped care pathways, none of which were for NTDs where preventive chemotherapy is the primary management strategy. The majority of studies (82.9%; 136/164) presented unmapped care pathways, which were primarily biomedical research studies that provided diagnosis and/or treatment of NTD patients (66.9%; 91/136). Of biomedical research studies, 36.3% (33/91) described strategies to support continuity of care. While there is no singular care pathway for all NTDs in SSA, we proposed a conceptual framework relevant for implementation of biomedical research. Interpretation: Further research is needed on morbidity management of NTDs typically addressed through mass drug administration in sub-Saharan Africa. To conduct this research, there is a need for guidance on how research sponsors should collaborate with local health systems to enable continuity of care in low-income, NTD-endemic settings.
{"title":"Conceptualising care pathways for neglected tropical diseases in sub-Saharan Africa: A systematic scoping review","authors":"Sandrena Ruth Frischer, Eloise S Ockenden, Fabian Reitzug, Michael Parker, Goylette F Chami","doi":"10.1101/2024.09.13.24313492","DOIUrl":"https://doi.org/10.1101/2024.09.13.24313492","url":null,"abstract":"Background: There is a lack of synthesized evidence on how best to support care continuity for neglected tropical diseases (NTDs) in sub-Saharan Africa (SSA). Methods: To identify all SSA NTD care pathways, we conducted a systematic search of six scientific databases from inception to 18 February 2023. All studies were required to include care pathways for NTDs, defined at minimum as having both NTD diagnosis and treatment or referral to treatment for care continuity. Using an iterative approach to establish an understanding of care pathways relevant for NTDs, concept development drew from data extraction of variables relating to study characteristics; approaches to diagnosis, treatment, and referrals as pathway components; barriers to care and strategies for their resolution; and ethical challenges. Findings: Searches returned 2178 studies where after de-duplication and eligibility screening, 164 were systematically reviewed. Medical referrals were used to support care continuity in 62.2% (102/164) of studies, and community health workers played roles in patient care in 22.6% (37/164) of studies. Only 6.7% (11/164) of studies explicitly mapped care pathways, none of which were for NTDs where preventive chemotherapy is the primary management strategy. The majority of studies (82.9%; 136/164) presented unmapped care pathways, which were primarily biomedical research studies that provided diagnosis and/or treatment of NTD patients (66.9%; 91/136). Of biomedical research studies, 36.3% (33/91) described strategies to support continuity of care. While there is no singular care pathway for all NTDs in SSA, we proposed a conceptual framework relevant for implementation of biomedical research. Interpretation: Further research is needed on morbidity management of NTDs typically addressed through mass drug administration in sub-Saharan Africa. To conduct this research, there is a need for guidance on how research sponsors should collaborate with local health systems to enable continuity of care in low-income, NTD-endemic settings.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265732","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 : 2024-09-13DOI: 10.1101/2024.09.11.24313421
Bokretsion G Brhane, Abebe A Fola, Helen Nigussie, Alec Leonetti, Moges Kassa, Henok Hailgiorgis, Yonas Wuletaw, Adugna Abera, Hussein Mohammed, Heven Sime, Abeba G/Tsadik, Gudissa Assefa, Hiwot Solomon, Geremew Tasew, Getachew Tollera, Mesay Hailu, Jonathan J Juliano, Ashenafi Assefa, Jonathan B Parr, Jeffrey A Bailey
Ethiopia is striving to eliminate local malaria transmission by 2030, despite a recent resurgence of malaria cases due to multiple factors. A significant contributor to this resurgence could be drug resistance, particularly the emergence of partial resistance to artemisinin (ArtR) in Ethiopia and other regions of Eastern Africa. This situation highlights the necessity for genomic surveillance to monitor relevant drug resistance markers. This study reports sentinel site-based genomic surveillance results for P. falciparum antimalarial drug resistance mutations. From 2019 to 2022, dried blood spots (DBS) were collected from febrile outpatients ≥1 year of age with microscopically confirmed falciparum malaria at 12 sentinel sites across 5 regions. Molecular inversion probe (MIP) sequencing targeted mutations associated with artemisinin and partner drug resistance, including k13, mdr1, crt, dhfr, and dhps genes, along with genome-wide markers to assess the complexity of infection (COI) and parasite relatedness. A total of 1,199 falciparum-positive patients were assessed, with a median age of 20 years (IQR: 14-30) and including 463 (38.6%) females. The WHO-validated K13 R622I mutation had a high but regionally variable prevalence (15.7%, range 0-58.8%). The validated K13 A675V mutation was detected for the first time in Ethiopia in the Gambella Region (4.5%), as well as P441L and P574L mutations were detected at low frequencies in Southern and Oromia Regions, respectively. Several partner drug resistance markers were identified, with mutations in MDR1(184F), DHPS, DHFR, and CRT nearly fixed across the country. Most samples (87.2%) were monogenic infections (COI=1) and showed high genetic relatedness, particularly within the health facilities. Principal component analysis revealed regional clustering of parasites, particularly in Gambella. The prevalence of K13 R622I across the country and the presence of multiple additional ArtR markers emphasizes the urgent need for rigorous monitoring of artemisinin combination therapy (ACT) efficacy to detect partner drug resistance and ACT failure early and its impact on malaria resurgence in Ethiopia.
{"title":"Rising prevalence of Plasmodium falciparum artemisinin resistance mutations in Ethiopia","authors":"Bokretsion G Brhane, Abebe A Fola, Helen Nigussie, Alec Leonetti, Moges Kassa, Henok Hailgiorgis, Yonas Wuletaw, Adugna Abera, Hussein Mohammed, Heven Sime, Abeba G/Tsadik, Gudissa Assefa, Hiwot Solomon, Geremew Tasew, Getachew Tollera, Mesay Hailu, Jonathan J Juliano, Ashenafi Assefa, Jonathan B Parr, Jeffrey A Bailey","doi":"10.1101/2024.09.11.24313421","DOIUrl":"https://doi.org/10.1101/2024.09.11.24313421","url":null,"abstract":"Ethiopia is striving to eliminate local malaria transmission by 2030, despite a recent resurgence of malaria cases due to multiple factors. A significant contributor to this resurgence could be drug resistance, particularly the emergence of partial resistance to artemisinin (ArtR) in Ethiopia and other regions of Eastern Africa. This situation highlights the necessity for genomic surveillance to monitor relevant drug resistance markers. This study reports sentinel site-based genomic surveillance results for <em>P. falciparum</em> antimalarial drug resistance mutations. From 2019 to 2022, dried blood spots (DBS) were collected from febrile outpatients ≥1 year of age with microscopically confirmed falciparum malaria at 12 sentinel sites across 5 regions. Molecular inversion probe (MIP) sequencing targeted mutations associated with artemisinin and partner drug resistance, including <em>k13</em>, <em>mdr1</em>, <em>crt</em>, <em>dhfr</em>, and <em>dhps</em> genes, along with genome-wide markers to assess the complexity of infection (COI) and parasite relatedness. A total of 1,199 falciparum-positive patients were assessed, with a median age of 20 years (IQR: 14-30) and including 463 (38.6%) females. The WHO-validated K13 R622I mutation had a high but regionally variable prevalence (15.7%, range 0-58.8%). The validated K13 A675V mutation was detected for the first time in Ethiopia in the Gambella Region (4.5%), as well as P441L and P574L mutations were detected at low frequencies in Southern and Oromia Regions, respectively. Several partner drug resistance markers were identified, with mutations in MDR1(184F), DHPS, DHFR, and CRT nearly fixed across the country. Most samples (87.2%) were monogenic infections (COI=1) and showed high genetic relatedness, particularly within the health facilities. Principal component analysis revealed regional clustering of parasites, particularly in Gambella. The prevalence of K13 R622I across the country and the presence of multiple additional ArtR markers emphasizes the urgent need for rigorous monitoring of artemisinin combination therapy (ACT) efficacy to detect partner drug resistance and ACT failure early and its impact on malaria resurgence in Ethiopia.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269786","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 : 2024-09-13DOI: 10.1101/2024.09.12.24313589
Khai Hoan Tram, Jane Rahedi Ong'ang'o, Richard Kiplimo, Thomas R. Hawn, Videlis Nduba, David J. Horne, Jennifer M. Ross
Background: Annually, over 3 million people develop TB but are not diagnosed and treated. We aimed to characterize the mobility patterns and activity locations of people with TB in an urban, high burden setting to inform future active case finding (ACF) efforts. Methods: We conducted a population based TB prevalence survey in Nairobi, Kenya, in 2022. Participants aged 15 years or older with TB symptoms or a suggestive chest x-ray submitted sputum for Xpert Ultra and culture. We collected data on individual activity locations and mobility and evaluated their association with the risk of pulmonary TB. Results: The prevalence survey enrolled 6369 participants across nine clusters. There were significant differences in mobility patterns and activity locations between sexes and age groups. Mobility factors were not significantly associated with TB. In the adjusted analysis, age group 45 to 54 (OR 2.45), male sex (OR 2.95), and use of a social activity location (OR 1.96) were significantly associated with a higher risk of TB. Conclusions: We did not find a significant association between mobility patterns and TB but found a positive association between reported "social" activity locations and TB. Identification of "social" activity locations, particularly bars, provides important insight into possible venues for spatially targeted ACF activities.
{"title":"Mobility patterns, activity locations, and tuberculosis in Nairobi, Kenya","authors":"Khai Hoan Tram, Jane Rahedi Ong'ang'o, Richard Kiplimo, Thomas R. Hawn, Videlis Nduba, David J. Horne, Jennifer M. Ross","doi":"10.1101/2024.09.12.24313589","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313589","url":null,"abstract":"Background:\u0000Annually, over 3 million people develop TB but are not diagnosed and treated. We aimed to characterize the mobility patterns and activity locations of people with TB in an urban, high burden setting to inform future active case finding (ACF) efforts. Methods:\u0000We conducted a population based TB prevalence survey in Nairobi, Kenya, in 2022. Participants aged 15 years or older with TB symptoms or a suggestive chest x-ray submitted sputum for Xpert Ultra and culture. We collected data on individual activity locations and mobility and evaluated their association with the risk of pulmonary TB. Results:\u0000The prevalence survey enrolled 6369 participants across nine clusters. There were significant differences in mobility patterns and activity locations between sexes and age groups. Mobility factors were not significantly associated with TB. In the adjusted analysis, age group 45 to 54 (OR 2.45), male sex (OR 2.95), and use of a social activity location (OR 1.96) were significantly associated with a higher risk of TB. Conclusions:\u0000We did not find a significant association between mobility patterns and TB but found a positive association between reported \"social\" activity locations and TB. Identification of \"social\" activity locations, particularly bars, provides important insight into possible venues for spatially targeted ACF activities.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142265734","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 : 2024-09-13DOI: 10.1101/2024.09.12.24313530
Constance Adu-Gyamfi, Jesse Addo Asamoah, James Opoku Frimpong, Richard Larbi, Richard Owusu Ansah, Sherihane Naa Ayeley Aryeetey, Richmond Gorman, Henry Kyeremateng Acheampong, Emmanuella Nyarko-Afriyie, Manuella Hayford, Henrietta Dede Tetteh, Kwadwo Boampong, Veronica Barnor, Peter K. Brenya, Frederick Ayensu, Nana Kwame Ayisi-Boateng, Philip El-Duah, Christian Drosten, Richard Odame Phillips, Augustina Angelina Sylverken, Michael Owusu
Introduction The COVID-19 pandemic has significantly affected healthcare systems worldwide, impacting the occurrence and management of respiratory illnesses. This has also influenced respiratory infections’ role in childhood mortality. Surveillance of common respiratory viruses in Ghana is limited, making it crucial to assess the prevalence of respiratory viral infections, particularly in children, in the post-pandemic era. This study aimed to determine the prevalence of respiratory viruses and identify associated risk factors in children aged 5 or younger in an urban paediatric hospital setting. Methods The study was a cross-sectional study with a convenience sampling method, conducted in four health facilities: Asokwa Children’s Hospital, HopeXchange Medical Centre, University Health Services-KNUST, and Kumasi South Hospital in Kumasi, Ghana, between August 2022 and June 2023. Recruitment was not done in parallel in each hospital. Oropharyngeal swabs were collected from children <= 5 years old and screened by RT-qPCR for common respiratory viruses. Results Out of the 303 patients enrolled in the study, 165 (54.4%) were male, and 122 (40.3%) were aged from 13 to 36 months. The median age of the patients was 19 months. The most common symptoms reported were cough (87.0%), runny nose (87.0%), and fever (72.0%). Respiratory viruses were detected in 100 (33.0%) of the samples, with 36 (12.0%) testing positive for Human metapneumovirus (HMPV), 27 (8.9%) for RSV, and 20 (6.6%) for Human Adenovirus (HAdV). In 8.0% of the cases, multiple viruses were detected, with HAdV being the most common (75.0%). Children under 6 months (AOR: 4.81, 95% CI: 1.20-24.60) had a higher risk of RSV detection compared to children aged 37 to 60 months. Furthermore, it was found that caregivers with tertiary education had a higher risk of HMPV detection (AOR: 6.91, 95% CI: 1.71-47.3). Conclusion The study's findings emphasize the potentially significant role of HMPV in causing respiratory infections among children in Ghana. Active surveillance of common respiratory viruses in healthcare facilities could enhance the management of viral respiratory infection cases in the paediatric population in Ghana.
{"title":"Prevalence of common respiratory viruses in children: insights from post-pandemic surveillance","authors":"Constance Adu-Gyamfi, Jesse Addo Asamoah, James Opoku Frimpong, Richard Larbi, Richard Owusu Ansah, Sherihane Naa Ayeley Aryeetey, Richmond Gorman, Henry Kyeremateng Acheampong, Emmanuella Nyarko-Afriyie, Manuella Hayford, Henrietta Dede Tetteh, Kwadwo Boampong, Veronica Barnor, Peter K. Brenya, Frederick Ayensu, Nana Kwame Ayisi-Boateng, Philip El-Duah, Christian Drosten, Richard Odame Phillips, Augustina Angelina Sylverken, Michael Owusu","doi":"10.1101/2024.09.12.24313530","DOIUrl":"https://doi.org/10.1101/2024.09.12.24313530","url":null,"abstract":"Introduction The COVID-19 pandemic has significantly affected healthcare systems worldwide, impacting the occurrence and management of respiratory illnesses. This has also influenced respiratory infections’ role in childhood mortality. Surveillance of common respiratory viruses in Ghana is limited, making it crucial to assess the prevalence of respiratory viral infections, particularly in children, in the post-pandemic era. This study aimed to determine the prevalence of respiratory viruses and identify associated risk factors in children aged 5 or younger in an urban paediatric hospital setting. Methods The study was a cross-sectional study with a convenience sampling method, conducted in four health facilities: Asokwa Children’s Hospital, HopeXchange Medical Centre, University Health Services-KNUST, and Kumasi South Hospital in Kumasi, Ghana, between August 2022 and June 2023. Recruitment was not done in parallel in each hospital. Oropharyngeal swabs were collected from children <= 5 years old and screened by RT-qPCR for common respiratory viruses. Results Out of the 303 patients enrolled in the study, 165 (54.4%) were male, and 122 (40.3%) were aged from 13 to 36 months. The median age of the patients was 19 months. The most common symptoms reported were cough (87.0%), runny nose (87.0%), and fever (72.0%). Respiratory viruses were detected in 100 (33.0%) of the samples, with 36 (12.0%) testing positive for Human metapneumovirus (HMPV), 27 (8.9%) for RSV, and 20 (6.6%) for Human Adenovirus (HAdV). In 8.0% of the cases, multiple viruses were detected, with HAdV being the most common (75.0%). Children under 6 months (AOR: 4.81, 95% CI: 1.20-24.60) had a higher risk of RSV detection compared to children aged 37 to 60 months. Furthermore, it was found that caregivers with tertiary education had a higher risk of HMPV detection (AOR: 6.91, 95% CI: 1.71-47.3). Conclusion The study's findings emphasize the potentially significant role of HMPV in causing respiratory infections among children in Ghana. Active surveillance of common respiratory viruses in healthcare facilities could enhance the management of viral respiratory infection cases in the paediatric population in Ghana.","PeriodicalId":501509,"journal":{"name":"medRxiv - Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142269787","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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