Kamran Badizadegan, Dominika A Kalkowska, Kimberly M Thompson
Background: Investments in national immunization programs and the Global Polio Eradication Initiative (GPEI) have resulted in substantial reductions in paralytic polio worldwide. However, cases prevented because of investments in immunization programs and GPEI remain incompletely characterized.
Methods: Using a global model that integrates polio transmission, immunity, and vaccine dynamics, we provide estimates of polio incidence and numbers of paralytic cases prevented. We compare the results with reported cases and estimates historically published by the World Health Organization.
Results: We estimate that the existence and use of polio vaccines prevented 5 million cases of paralytic polio for 1960-1987 and 24 million cases worldwide for 1988-2021 compared to a counterfactual world with no polio vaccines. Since the 1988 resolution to eradicate polio, our estimates suggest GPEI prevented 2.5-6 million cases of paralytic polio compared to counterfactual worlds without GPEI that assume different levels of intensity of polio vaccine use in routine immunization programs.
Conclusions: Analysis of historical cases provides important context for understanding and communicating the benefits of investments made in polio eradication. Prospective studies will need to explore the expected benefits of future investments, the outcomes of which will depend on whether and when polio is globally eradicated.
{"title":"Polio by the Numbers-A Global Perspective.","authors":"Kamran Badizadegan, Dominika A Kalkowska, Kimberly M Thompson","doi":"10.1093/infdis/jiac130","DOIUrl":"10.1093/infdis/jiac130","url":null,"abstract":"<p><strong>Background: </strong>Investments in national immunization programs and the Global Polio Eradication Initiative (GPEI) have resulted in substantial reductions in paralytic polio worldwide. However, cases prevented because of investments in immunization programs and GPEI remain incompletely characterized.</p><p><strong>Methods: </strong>Using a global model that integrates polio transmission, immunity, and vaccine dynamics, we provide estimates of polio incidence and numbers of paralytic cases prevented. We compare the results with reported cases and estimates historically published by the World Health Organization.</p><p><strong>Results: </strong>We estimate that the existence and use of polio vaccines prevented 5 million cases of paralytic polio for 1960-1987 and 24 million cases worldwide for 1988-2021 compared to a counterfactual world with no polio vaccines. Since the 1988 resolution to eradicate polio, our estimates suggest GPEI prevented 2.5-6 million cases of paralytic polio compared to counterfactual worlds without GPEI that assume different levels of intensity of polio vaccine use in routine immunization programs.</p><p><strong>Conclusions: </strong>Analysis of historical cases provides important context for understanding and communicating the benefits of investments made in polio eradication. Prospective studies will need to explore the expected benefits of future investments, the outcomes of which will depend on whether and when polio is globally eradicated.</p>","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"44 1","pages":"1309-1318"},"PeriodicalIF":0.0,"publicationDate":"2022-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81286799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-10-04DOI: 10.1101/2022.10.04.22280689
Kayoko Shioda, Yang-ling Chen, M. Collins, B. Lopman
Background: Immune protection against SARS-CoV-2 can be induced by natural infection or vaccination or both. The interaction between vaccine-induced immunity and naturally acquired immunity at the population level has been understudied. Methods: We used regression models to evaluate whether the impact of COVID-19 vaccines differed across states with different levels of naturally acquired immunity from March 2021 to April 2022 in the United States. Analysis was conducted for three evaluation periods separately (Alpha, Delta, and Omicron waves). As a proxy of the proportion of the population with naturally acquired immunity, we used either the reported seroprevalence or the estimated proportion of the population ever infected in each state. Results: COVID-19 mortality decreased as the coverage of [≥]1 dose increased among people [≥]65 years of age, and this effect did not vary by seroprevalence or the proportion of the total population ever infected. Seroprevalence and the proportion ever infected were not associated with COVID-19 mortality, after controlling for vaccine coverage. These findings were consistent in all evaluation periods. Conclusions: COVID-19 vaccination was associated with a sustained reduction in mortality at the state level during the Alpha, Delta, and Omicron periods. The effect did not vary by naturally acquired immunity.
{"title":"Population-level relative effectiveness of the COVID-19 vaccines and the contribution of naturally acquired immunity","authors":"Kayoko Shioda, Yang-ling Chen, M. Collins, B. Lopman","doi":"10.1101/2022.10.04.22280689","DOIUrl":"https://doi.org/10.1101/2022.10.04.22280689","url":null,"abstract":"Background: Immune protection against SARS-CoV-2 can be induced by natural infection or vaccination or both. The interaction between vaccine-induced immunity and naturally acquired immunity at the population level has been understudied. Methods: We used regression models to evaluate whether the impact of COVID-19 vaccines differed across states with different levels of naturally acquired immunity from March 2021 to April 2022 in the United States. Analysis was conducted for three evaluation periods separately (Alpha, Delta, and Omicron waves). As a proxy of the proportion of the population with naturally acquired immunity, we used either the reported seroprevalence or the estimated proportion of the population ever infected in each state. Results: COVID-19 mortality decreased as the coverage of [≥]1 dose increased among people [≥]65 years of age, and this effect did not vary by seroprevalence or the proportion of the total population ever infected. Seroprevalence and the proportion ever infected were not associated with COVID-19 mortality, after controlling for vaccine coverage. These findings were consistent in all evaluation periods. Conclusions: COVID-19 vaccination was associated with a sustained reduction in mortality at the state level during the Alpha, Delta, and Omicron periods. The effect did not vary by naturally acquired immunity.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85878022","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 : 2022-09-30DOI: 10.1101/2022.09.29.22280526
R. Grewal, Leann Nguyen, S. Buchan, S. Wilson, Andrew P Costa, Jeffrey C Kwong
Background: As of December 30, 2021, Ontario long-term care (LTC) residents who received a third dose of COVID-19 vaccine [≥]84 days previously were offered a fourth dose to prevent a surge in COVID-19-related morbidity and mortality due to the Omicron variant. Seven months have passed since fourth doses were implemented, allowing for the examination of fourth dose protection over time. Methods: We used a test-negative design and linked databases to estimate the marginal effectiveness (4 versus 3 doses) and vaccine effectiveness (VE; 2, 3, or 4 doses versus no doses) of mRNA vaccines among Ontario LTC residents aged [≥]60 years who were tested for SARS-CoV-2 between December 30, 2021 and August 3, 2022. Outcome measures included any Omicron infection, symptomatic infection, and severe outcomes (hospitalization or death). Results: We included 21,275 Omicron cases and 273,466 test-negative controls. The marginal effectiveness of a fourth dose <84 days ago compared to a third dose received [≥]84 days ago was 23% (95% Confidence Interval [CI] 17-29%), 36% (95%CI 26-44%), and 37% (95%CI 24-48%) against SARS-CoV-2 infection, symptomatic infection, and severe outcomes, respectively. Additional protection provided by a fourth dose compared to a third dose was negligible against all outcomes [≥]168 days after vaccination. Compared to unvaccinated individuals, vaccine effectiveness (VE) of a fourth dose decreased from 49% (95%CI 44%-54%) to 18% (95%CI 5-28%) against infection, 69% (95%CI 62-75%) to 44% (95%CI 24-59%) against symptomatic infection, and 82% (95%CI 77-86%) to 74% (95%CI 62-82%) against severe outcomes <84 days versus [≥]168 days after vaccination. Conclusions: Our findings suggest that fourth doses of mRNA COVID-19 vaccines provide additional protection against Omicron-related outcomes in LTC residents, but the protection wanes over time, with more waning seen against infection than severe outcomes.
{"title":"Effectiveness and Duration of Protection of a Fourth Dose of COVID-19 mRNA Vaccine among Long-Term Care Residents in Ontario, Canada","authors":"R. Grewal, Leann Nguyen, S. Buchan, S. Wilson, Andrew P Costa, Jeffrey C Kwong","doi":"10.1101/2022.09.29.22280526","DOIUrl":"https://doi.org/10.1101/2022.09.29.22280526","url":null,"abstract":"Background: As of December 30, 2021, Ontario long-term care (LTC) residents who received a third dose of COVID-19 vaccine [≥]84 days previously were offered a fourth dose to prevent a surge in COVID-19-related morbidity and mortality due to the Omicron variant. Seven months have passed since fourth doses were implemented, allowing for the examination of fourth dose protection over time. Methods: We used a test-negative design and linked databases to estimate the marginal effectiveness (4 versus 3 doses) and vaccine effectiveness (VE; 2, 3, or 4 doses versus no doses) of mRNA vaccines among Ontario LTC residents aged [≥]60 years who were tested for SARS-CoV-2 between December 30, 2021 and August 3, 2022. Outcome measures included any Omicron infection, symptomatic infection, and severe outcomes (hospitalization or death). Results: We included 21,275 Omicron cases and 273,466 test-negative controls. The marginal effectiveness of a fourth dose <84 days ago compared to a third dose received [≥]84 days ago was 23% (95% Confidence Interval [CI] 17-29%), 36% (95%CI 26-44%), and 37% (95%CI 24-48%) against SARS-CoV-2 infection, symptomatic infection, and severe outcomes, respectively. Additional protection provided by a fourth dose compared to a third dose was negligible against all outcomes [≥]168 days after vaccination. Compared to unvaccinated individuals, vaccine effectiveness (VE) of a fourth dose decreased from 49% (95%CI 44%-54%) to 18% (95%CI 5-28%) against infection, 69% (95%CI 62-75%) to 44% (95%CI 24-59%) against symptomatic infection, and 82% (95%CI 77-86%) to 74% (95%CI 62-82%) against severe outcomes <84 days versus [≥]168 days after vaccination. Conclusions: Our findings suggest that fourth doses of mRNA COVID-19 vaccines provide additional protection against Omicron-related outcomes in LTC residents, but the protection wanes over time, with more waning seen against infection than severe outcomes.","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90573292","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}
Shelly Bolotin, Selma Osman, Stephanie L Hughes, Archchun Ariyarajah, Andrea C Tricco, Sumaiya Khan, Lennon Li, Caitlin Johnson, Lindsay Friedman, Nazish Gul, Rachel Jardine, Maryrose Faulkner, Susan J M Hahné, Jane M Heffernan, Alya Dabbagh, Paul A Rota, Alberto Severini, Mark Jit, David N Durrheim, Walter A Orenstein, William J Moss, Sebastian Funk, Nikki Turner, William Schluter, Jaleela S Jawad, Natasha S Crowcroft
Background: We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings.
Methods: After screening 16 822 citations, we identified 9 articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria.
Results: Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], -212.4 to -31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, -95.3 to -12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, -62.6 to -3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, -51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection.
Conclusions: Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.
{"title":"In Elimination Settings, Measles Antibodies Wane After Vaccination but Not After Infection: A Systematic Review and Meta-Analysis.","authors":"Shelly Bolotin, Selma Osman, Stephanie L Hughes, Archchun Ariyarajah, Andrea C Tricco, Sumaiya Khan, Lennon Li, Caitlin Johnson, Lindsay Friedman, Nazish Gul, Rachel Jardine, Maryrose Faulkner, Susan J M Hahné, Jane M Heffernan, Alya Dabbagh, Paul A Rota, Alberto Severini, Mark Jit, David N Durrheim, Walter A Orenstein, William J Moss, Sebastian Funk, Nikki Turner, William Schluter, Jaleela S Jawad, Natasha S Crowcroft","doi":"10.1093/infdis/jiac039","DOIUrl":"10.1093/infdis/jiac039","url":null,"abstract":"<p><strong>Background: </strong>We conducted a systematic review to assess whether measles humoral immunity wanes in previously infected or vaccinated populations in measles elimination settings.</p><p><strong>Methods: </strong>After screening 16 822 citations, we identified 9 articles from populations exposed to wild-type measles and 16 articles from vaccinated populations that met our inclusion criteria.</p><p><strong>Results: </strong>Using linear regression, we found that geometric mean titers (GMTs) decreased significantly in individuals who received 2 doses of measles-containing vaccine (MCV) by 121.8 mIU/mL (95% confidence interval [CI], -212.4 to -31.1) per year since vaccination over 1 to 5 years, 53.7 mIU/mL (95% CI, -95.3 to -12.2) 5 to 10 years, 33.2 mIU/mL (95% CI, -62.6 to -3.9), 10 to 15 years, and 24.1 mIU/mL (95% CI, -51.5 to 3.3) 15 to 20 years since vaccination. Decreases in GMT over time were not significant after 1 dose of MCV or after infection. Decreases in the proportion of seropositive individuals over time were not significant after 1 or 2 doses of MCV or after infection.</p><p><strong>Conclusions: </strong>Measles antibody waning in vaccinated populations should be considered in planning for measles elimination.</p>","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"62 1","pages":"1127-1139"},"PeriodicalIF":0.0,"publicationDate":"2022-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81262896","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}
Audrey E Rindler, Katharina Kusejko, Herbert Kuster, Kathrin Neumann, Christine Leemann, Marius Zeeb, Sandra E Chaudron, Dominique L Braun, Roger D Kouyos, Karin J Metzner, Huldrych F Günthard
Background: HIV-1 replication capacity (RC) of transmitted/founder viruses may influence the further course of HIV-1 infection.
Methods: RCs of 355 whole-genome primary HIV-1 isolates derived from samples acquired during acute and recent primary HIV-1 infection (PHI) were determined using a novel high-throughput infection assay in primary cells. The RCs were used to elucidate potential factors that could be associated with RC during PHI.
Results: Increased RC was found to be associated with increased set point viral load (VL), and significant differences in RCs among 13 different HIV-1 subtypes were discerned. Notably, we observed an increase in RCs for primary HIV-1 isolates of HIV-1 subtype B over a 17-year period. Associations were not observed between RC and CD4 count at sample date of RC measurement, CD4 recovery after initiation of antiretroviral treatment, CD4 decline in untreated individuals, and acute retroviral syndrome severity scores.
Conclusions: These findings highlight that RCs of primary HIV-1 isolates acquired during the acute and recent phase of infection are more associated with viral factors, that is set point VL, than with host factors. Furthermore, we observed a temporal increase in RC for HIV-1 subtype B viruses over a period of 17 years.
{"title":"The Interplay Between Replication Capacity of HIV-1 and Surrogate Markers of Disease.","authors":"Audrey E Rindler, Katharina Kusejko, Herbert Kuster, Kathrin Neumann, Christine Leemann, Marius Zeeb, Sandra E Chaudron, Dominique L Braun, Roger D Kouyos, Karin J Metzner, Huldrych F Günthard","doi":"10.1093/infdis/jiac100","DOIUrl":"10.1093/infdis/jiac100","url":null,"abstract":"<p><strong>Background: </strong>HIV-1 replication capacity (RC) of transmitted/founder viruses may influence the further course of HIV-1 infection.</p><p><strong>Methods: </strong>RCs of 355 whole-genome primary HIV-1 isolates derived from samples acquired during acute and recent primary HIV-1 infection (PHI) were determined using a novel high-throughput infection assay in primary cells. The RCs were used to elucidate potential factors that could be associated with RC during PHI.</p><p><strong>Results: </strong>Increased RC was found to be associated with increased set point viral load (VL), and significant differences in RCs among 13 different HIV-1 subtypes were discerned. Notably, we observed an increase in RCs for primary HIV-1 isolates of HIV-1 subtype B over a 17-year period. Associations were not observed between RC and CD4 count at sample date of RC measurement, CD4 recovery after initiation of antiretroviral treatment, CD4 decline in untreated individuals, and acute retroviral syndrome severity scores.</p><p><strong>Conclusions: </strong>These findings highlight that RCs of primary HIV-1 isolates acquired during the acute and recent phase of infection are more associated with viral factors, that is set point VL, than with host factors. Furthermore, we observed a temporal increase in RC for HIV-1 subtype B viruses over a period of 17 years.</p><p><strong>Clinical trials registration: </strong>NCT00537966.</p>","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"27 1","pages":"1057-1068"},"PeriodicalIF":0.0,"publicationDate":"2022-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89897645","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}
N F Walker, F Karim, M Y S Moosa, S Moodley, M Mazibuko, K Khan, T R Sterling, Y F van der Heijden, A D Grant, P T Elkington, A Pym, A Leslie
Current methods for tuberculosis treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during tuberculosis treatment as biomarkers. Plasma MMP-1, MMP-8, and MMP-10 concentrations significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture-positive relative to culture-negative participants, before (median, 4993 pg/mL [interquartile range, 2542-9188] vs 698 [218-4060] pg/mL, respectively; P = .004) and after (3650 [1214-3888] vs 720 [551-1321] pg/mL; P = .008) 6 months of tuberculosis treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance tuberculosis treatment monitoring and screen for possible culture positivity.
{"title":"Elevated Plasma Matrix Metalloproteinase 8 Associates With Sputum Culture Positivity in Pulmonary Tuberculosis.","authors":"N F Walker, F Karim, M Y S Moosa, S Moodley, M Mazibuko, K Khan, T R Sterling, Y F van der Heijden, A D Grant, P T Elkington, A Pym, A Leslie","doi":"10.1093/infdis/jiac160","DOIUrl":"10.1093/infdis/jiac160","url":null,"abstract":"<p><p>Current methods for tuberculosis treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during tuberculosis treatment as biomarkers. Plasma MMP-1, MMP-8, and MMP-10 concentrations significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture-positive relative to culture-negative participants, before (median, 4993 pg/mL [interquartile range, 2542-9188] vs 698 [218-4060] pg/mL, respectively; P = .004) and after (3650 [1214-3888] vs 720 [551-1321] pg/mL; P = .008) 6 months of tuberculosis treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance tuberculosis treatment monitoring and screen for possible culture positivity.</p>","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"29 1","pages":"928-932"},"PeriodicalIF":0.0,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9470104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75385123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ankur Sharma, Bethany Jenkins, Adovi Akue, Lynn E Lambert, Sachy Orr-Gonzalez, Marvin L Thomas, Almahamoudou Mahamar, Bacary S Diarra, Alassane Dicko, Michal Fried, Patrick E Duffy
Plasmodium falciparum-infected erythrocytes that display the variant surface antigen VAR2CSA bind chondroitin sulfate A (CSA) to sequester in placental intervillous spaces, causing severe sequelae for mother and offspring. Here, we establish a placental malaria (PM) monkey model. Pregnant Aotus infected with CSA-binding P. falciparum CS2 parasites during the third trimester developed pronounced sequestration of late-stage parasites in placental intervillous spaces that express VAR2CSA and bind specifically to CSA. Similar to immune multigravid women, a monkey infected with P. falciparum CS2 parasites over successive pregnancies acquired antibodies against VAR2CSA, with potent functional activity that was boosted upon subsequent pregnancy infections. Aotus also developed functional antibodies after multiple acute PM episodes and subsequent VAR2CSA immunization. In summary, P. falciparum infections in pregnant Aotus monkeys recapitulate all the prominent features of human PM infection and immunity, and this model can be useful for basic mechanistic studies and preclinical studies to qualify candidate PM vaccines. Clinical Trials Registration: NCT02471378.
{"title":"Plasmodium falciparum in Aotus nancymaae: A New Model for Placental Malaria.","authors":"Ankur Sharma, Bethany Jenkins, Adovi Akue, Lynn E Lambert, Sachy Orr-Gonzalez, Marvin L Thomas, Almahamoudou Mahamar, Bacary S Diarra, Alassane Dicko, Michal Fried, Patrick E Duffy","doi":"10.1093/infdis/jiac096","DOIUrl":"10.1093/infdis/jiac096","url":null,"abstract":"<p><p>Plasmodium falciparum-infected erythrocytes that display the variant surface antigen VAR2CSA bind chondroitin sulfate A (CSA) to sequester in placental intervillous spaces, causing severe sequelae for mother and offspring. Here, we establish a placental malaria (PM) monkey model. Pregnant Aotus infected with CSA-binding P. falciparum CS2 parasites during the third trimester developed pronounced sequestration of late-stage parasites in placental intervillous spaces that express VAR2CSA and bind specifically to CSA. Similar to immune multigravid women, a monkey infected with P. falciparum CS2 parasites over successive pregnancies acquired antibodies against VAR2CSA, with potent functional activity that was boosted upon subsequent pregnancy infections. Aotus also developed functional antibodies after multiple acute PM episodes and subsequent VAR2CSA immunization. In summary, P. falciparum infections in pregnant Aotus monkeys recapitulate all the prominent features of human PM infection and immunity, and this model can be useful for basic mechanistic studies and preclinical studies to qualify candidate PM vaccines. Clinical Trials Registration: NCT02471378.</p>","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"8 1","pages":"521-527"},"PeriodicalIF":0.0,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9417121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80235033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Katrin Hartmann, Johannes G Liese, Daniel Kemmling, Christiane Prifert, Benedikt Weißbrich, Pushpike Thilakarathne, Joris Diels, Karin Weber, Andrea Streng
Background: Respiratory syncytial virus (RSV) is a leading cause of hospitalizations in children (≤5 years of age); limited data compare burden by age.
Methods: This single-center retrospective study included children (≤5 years of age) hospitalized for >24 hours with reverse-transcription polymerase chain reaction (RT-PCR)-confirmed RSV infection (2015-2018). Hospital length of stay (LOS), intensive care unit (ICU) admissions, ICU LOS, supplemental oxygen, and medication use were assessed. Multivariate logistic regression analyses identified predictors of hospital LOS >5 days.
Results: Three hundred twelve patients had RSV infection (ages 0 to <6 months [35%], 6 to <12 months [15%], 1 to <2 years [25%], and 2-5 years [25%]); 16.3% had predefined comorbidities (excludes preterm infants). Median hospital LOS was 5.0 days and similar across age; 5.1% (16/312) were admitted to ICU (ICU LOS, 5.0 days), with those aged 0 to <6 months admitted most frequently (10/108 [9.3%]). Supplemental oxygen was administered in 57.7% of patients, with similar need across ages. Antibiotics were administered frequently during hospitalization (43.6%). Predictors of prolonged LOS included pneumonia (odds ratio [OR], 2.33), supplemental oxygen need (OR, 5.09), and preterm births (OR, 3.37). High viral load (RT-PCR RSV cycle threshold value <25) was associated with greater need for supplemental oxygen.
Conclusions: RSV causes substantial burden in hospitalized children (≤5 years), particularly preterm infants and those aged <6 months.
{"title":"Clinical Burden of Respiratory Syncytial Virus in Hospitalized Children Aged ≤5 Years (INSPIRE Study).","authors":"Katrin Hartmann, Johannes G Liese, Daniel Kemmling, Christiane Prifert, Benedikt Weißbrich, Pushpike Thilakarathne, Joris Diels, Karin Weber, Andrea Streng","doi":"10.1093/infdis/jiac137","DOIUrl":"10.1093/infdis/jiac137","url":null,"abstract":"<p><strong>Background: </strong>Respiratory syncytial virus (RSV) is a leading cause of hospitalizations in children (≤5 years of age); limited data compare burden by age.</p><p><strong>Methods: </strong>This single-center retrospective study included children (≤5 years of age) hospitalized for >24 hours with reverse-transcription polymerase chain reaction (RT-PCR)-confirmed RSV infection (2015-2018). Hospital length of stay (LOS), intensive care unit (ICU) admissions, ICU LOS, supplemental oxygen, and medication use were assessed. Multivariate logistic regression analyses identified predictors of hospital LOS >5 days.</p><p><strong>Results: </strong>Three hundred twelve patients had RSV infection (ages 0 to <6 months [35%], 6 to <12 months [15%], 1 to <2 years [25%], and 2-5 years [25%]); 16.3% had predefined comorbidities (excludes preterm infants). Median hospital LOS was 5.0 days and similar across age; 5.1% (16/312) were admitted to ICU (ICU LOS, 5.0 days), with those aged 0 to <6 months admitted most frequently (10/108 [9.3%]). Supplemental oxygen was administered in 57.7% of patients, with similar need across ages. Antibiotics were administered frequently during hospitalization (43.6%). Predictors of prolonged LOS included pneumonia (odds ratio [OR], 2.33), supplemental oxygen need (OR, 5.09), and preterm births (OR, 3.37). High viral load (RT-PCR RSV cycle threshold value <25) was associated with greater need for supplemental oxygen.</p><p><strong>Conclusions: </strong>RSV causes substantial burden in hospitalized children (≤5 years), particularly preterm infants and those aged <6 months.</p>","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"7 1","pages":"386-395"},"PeriodicalIF":0.0,"publicationDate":"2022-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9417125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90320298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Julia C Cutts, Katherine O'Flaherty, Sophie G Zaloumis, Elizabeth A Ashley, Jo Anne Chan, Marie A Onyamboko, Caterina Fanello, Arjen M Dondorp, Nicholas P Day, Aung Pyae Phyo, Mehul Dhorda, Mallika Imwong, Rick M Fairhurst, Pharath Lim, Chanaki Amaratunga, Sasithon Pukrittayakamee, Tran Tinh Hien, Ye Htut, Mayfong Mayxay, M Abdul Faiz, Eizo Takashima, Takafumi Tsuboi, James G Beeson, Francois Nosten, Julie A Simpson, Nicholas J White, Freya J I Fowkes
Background: Understanding the effect of immunity on Plasmodium falciparum clearance is essential for interpreting therapeutic efficacy studies designed to monitor emergence of artemisinin drug resistance. In low-transmission areas of Southeast Asia, where resistance has emerged, P. falciparum antibodies confound parasite clearance measures. However, variation in naturally acquired antibodies across Asian and sub-Saharan African epidemiological contexts and their impact on parasite clearance re yet to be quantified.
Methods: In an artemisinin therapeutic efficacy study, antibodies to 12 pre-erythrocytic and erythrocytic P. falciparum antigens were measured in 118 children with uncomplicated P. falciparum malaria in the Democratic Republic of Congo (DRC) and compared with responses in patients from Asian sites, described elsewhere.
Results: Parasite clearance half-life was shorter in DRC patients (median, 2 hours) compared with most Asian sites (median, 2-7 hours), but P. falciparum antibody levels and seroprevalences were similar. There was no evidence for an association between antibody seropositivity and parasite clearance half-life (mean difference between seronegative and seropositive, -0.14 to +0.40 hour) in DRC patients.
Conclusions: In DRC, where artemisinin remains highly effective, the substantially shorter parasite clearance time compared with Asia was not explained by differences in the P. falciparum antibody responses studied.
{"title":"Comparison of Antibody Responses and Parasite Clearance in Artemisinin Therapeutic Efficacy Studies in the Democratic Republic of Congo and Asia.","authors":"Julia C Cutts, Katherine O'Flaherty, Sophie G Zaloumis, Elizabeth A Ashley, Jo Anne Chan, Marie A Onyamboko, Caterina Fanello, Arjen M Dondorp, Nicholas P Day, Aung Pyae Phyo, Mehul Dhorda, Mallika Imwong, Rick M Fairhurst, Pharath Lim, Chanaki Amaratunga, Sasithon Pukrittayakamee, Tran Tinh Hien, Ye Htut, Mayfong Mayxay, M Abdul Faiz, Eizo Takashima, Takafumi Tsuboi, James G Beeson, Francois Nosten, Julie A Simpson, Nicholas J White, Freya J I Fowkes","doi":"10.1093/infdis/jiac232","DOIUrl":"10.1093/infdis/jiac232","url":null,"abstract":"<p><strong>Background: </strong>Understanding the effect of immunity on Plasmodium falciparum clearance is essential for interpreting therapeutic efficacy studies designed to monitor emergence of artemisinin drug resistance. In low-transmission areas of Southeast Asia, where resistance has emerged, P. falciparum antibodies confound parasite clearance measures. However, variation in naturally acquired antibodies across Asian and sub-Saharan African epidemiological contexts and their impact on parasite clearance re yet to be quantified.</p><p><strong>Methods: </strong>In an artemisinin therapeutic efficacy study, antibodies to 12 pre-erythrocytic and erythrocytic P. falciparum antigens were measured in 118 children with uncomplicated P. falciparum malaria in the Democratic Republic of Congo (DRC) and compared with responses in patients from Asian sites, described elsewhere.</p><p><strong>Results: </strong>Parasite clearance half-life was shorter in DRC patients (median, 2 hours) compared with most Asian sites (median, 2-7 hours), but P. falciparum antibody levels and seroprevalences were similar. There was no evidence for an association between antibody seropositivity and parasite clearance half-life (mean difference between seronegative and seropositive, -0.14 to +0.40 hour) in DRC patients.</p><p><strong>Conclusions: </strong>In DRC, where artemisinin remains highly effective, the substantially shorter parasite clearance time compared with Asia was not explained by differences in the P. falciparum antibody responses studied.</p>","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"65 1","pages":"324-331"},"PeriodicalIF":0.0,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9400417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85800569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kristina L Bajema, Ryan Gierke, Monica M Farley, William Schaffner, Ann Thomas, Arthur L Reingold, Lee H Harrison, Ruth Lynfield, Kari E Burzlaff, Susan Petit, Meghan Barnes, Salina Torres, Paula M Snippes Vagnone, Bernard Beall, Tamara Pilishvili
Background: Antibiotic-nonsusceptible invasive pneumococcal disease (NS-IPD) incidence declined dramatically in the United States after introduction of pneumococcal conjugate vaccines (PCVs) into the infant immunization schedule (7-valent PCV7 in 2000, replaced by the 13-valent PCV13 in 2010). We evaluated the long-term impact of PCVs on NS-IPD.
Methods: We identified IPD cases through the Centers for Disease Control Active Bacterial Core surveillance during 1998-2018. Isolates intermediate or resistant to ≥1 antibiotic class were classified as nonsusceptible. We calculated annual rates of IPD (cases per 100 000 persons).
Results: From 1998 through 2018, NS-IPD incidence decreased from 43.9 to 3.2 among children <5 years and from 19.8 to 9.4 among adults ≥65 years. Incidence of vaccine-type NS-IPD decreased in all age groups, whereas incidence of nonvaccine type (NVT) NS-IPD increased in all age groups; the greatest absolute increase in NVT NS-IPD occurred among adults ≥65 years (2.3 to 7.2). During 2014-2018, NVTs 35B, 33F, 22F, and 15A were the most common NS-IPD serotypes.
Conclusions: Nonsusceptible IPD incidence decreased after PCV7 and PCV13 introduction in the United States. However, recent increases in NVT NS-IPD, most pronounced among older adults, have been observed. New higher valency PCVs containing the most common nonsusceptible serotypes, including 22F and 33F, could help further reduce NS-IPD.
{"title":"Impact of Pneumococcal Conjugate Vaccines on Antibiotic-Nonsusceptible Invasive Pneumococcal Disease in the United States.","authors":"Kristina L Bajema, Ryan Gierke, Monica M Farley, William Schaffner, Ann Thomas, Arthur L Reingold, Lee H Harrison, Ruth Lynfield, Kari E Burzlaff, Susan Petit, Meghan Barnes, Salina Torres, Paula M Snippes Vagnone, Bernard Beall, Tamara Pilishvili","doi":"10.1093/infdis/jiac154","DOIUrl":"10.1093/infdis/jiac154","url":null,"abstract":"<p><strong>Background: </strong>Antibiotic-nonsusceptible invasive pneumococcal disease (NS-IPD) incidence declined dramatically in the United States after introduction of pneumococcal conjugate vaccines (PCVs) into the infant immunization schedule (7-valent PCV7 in 2000, replaced by the 13-valent PCV13 in 2010). We evaluated the long-term impact of PCVs on NS-IPD.</p><p><strong>Methods: </strong>We identified IPD cases through the Centers for Disease Control Active Bacterial Core surveillance during 1998-2018. Isolates intermediate or resistant to ≥1 antibiotic class were classified as nonsusceptible. We calculated annual rates of IPD (cases per 100 000 persons).</p><p><strong>Results: </strong>From 1998 through 2018, NS-IPD incidence decreased from 43.9 to 3.2 among children <5 years and from 19.8 to 9.4 among adults ≥65 years. Incidence of vaccine-type NS-IPD decreased in all age groups, whereas incidence of nonvaccine type (NVT) NS-IPD increased in all age groups; the greatest absolute increase in NVT NS-IPD occurred among adults ≥65 years (2.3 to 7.2). During 2014-2018, NVTs 35B, 33F, 22F, and 15A were the most common NS-IPD serotypes.</p><p><strong>Conclusions: </strong>Nonsusceptible IPD incidence decreased after PCV7 and PCV13 introduction in the United States. However, recent increases in NVT NS-IPD, most pronounced among older adults, have been observed. New higher valency PCVs containing the most common nonsusceptible serotypes, including 22F and 33F, could help further reduce NS-IPD.</p>","PeriodicalId":22572,"journal":{"name":"The Indonesian Journal of Infectious Diseases","volume":"7 1","pages":"342-351"},"PeriodicalIF":0.0,"publicationDate":"2022-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74948303","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}