Mayimuna Nalubega, Megan S F Soon, Dean Andrew, Amaya Ortega-Pajares, Jessica Canning, Nicholas Dooley, Jessica R Loughland, Christian Engwerda, Enny Kenangalem, Ric N Price, Gabriela Minigo, Nicholas M Anstey, Damian A Oyong, Michelle J Boyle
Background Plasmodium falciparum and P. vivax are parasites responsible for most malaria cases globally. In areas where these species co-exist, individuals gain protection from P. vivax more rapidly, and important biological differences between species may impact the immune response. CD4 T cells are key drivers of immunity to malaria, both as effector and helper cells, with T-follicular helper (Tfh) cells having key roles in antibody development. Comparative studies on CD4 T cell responses between these species are limited. Methods We assessed CD4 T cells in adults with either P. falciparum or P. vivax malaria. Activation and proliferation of CD4 T cells were measured ex vivo, and functional capacity was determined by intracellular cytokine staining using flow cytometry. Results The phenotype, activation and proliferation of CD4 T cells and effector CD4 T cell subsets were comparable between species. However, within the peripheral (p)Tfh cell compartment, there was some evidence for species-dependent activation with relative increased pTfh1 cells in P. falciparum infection. Additionally, in P. falciparum, increased IL-10 production was detected, including within IL-21 producing CD4 T cells. Conclusion While activation and function of CD4 T cells in malaria are largely comparable, some species-dependent responses are detected within the pTfh cell compartment that may impact antibody development.
{"title":"Comparison of CD4 T cell response in Plasmodium falciparum and vivax malaria","authors":"Mayimuna Nalubega, Megan S F Soon, Dean Andrew, Amaya Ortega-Pajares, Jessica Canning, Nicholas Dooley, Jessica R Loughland, Christian Engwerda, Enny Kenangalem, Ric N Price, Gabriela Minigo, Nicholas M Anstey, Damian A Oyong, Michelle J Boyle","doi":"10.1093/infdis/jiag115","DOIUrl":"https://doi.org/10.1093/infdis/jiag115","url":null,"abstract":"Background Plasmodium falciparum and P. vivax are parasites responsible for most malaria cases globally. In areas where these species co-exist, individuals gain protection from P. vivax more rapidly, and important biological differences between species may impact the immune response. CD4 T cells are key drivers of immunity to malaria, both as effector and helper cells, with T-follicular helper (Tfh) cells having key roles in antibody development. Comparative studies on CD4 T cell responses between these species are limited. Methods We assessed CD4 T cells in adults with either P. falciparum or P. vivax malaria. Activation and proliferation of CD4 T cells were measured ex vivo, and functional capacity was determined by intracellular cytokine staining using flow cytometry. Results The phenotype, activation and proliferation of CD4 T cells and effector CD4 T cell subsets were comparable between species. However, within the peripheral (p)Tfh cell compartment, there was some evidence for species-dependent activation with relative increased pTfh1 cells in P. falciparum infection. Additionally, in P. falciparum, increased IL-10 production was detected, including within IL-21 producing CD4 T cells. Conclusion While activation and function of CD4 T cells in malaria are largely comparable, some species-dependent responses are detected within the pTfh cell compartment that may impact antibody development.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"48 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147292741","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}
Veronica A Pinell-McNamara, Hamed S Ouédraogo, Lassane Kafando, Ousmane Sani, Aichatou Arzika Issoufou, Elhadji Ibrahim Tassiou, Mahamoudou Sanou, Felix Tarbangdo, Andre Bita, Katya Fernandez, Joann Kekeisen-Chen, Natacha Cureau, Adakal Aboubacar, Frédérick Acho, Flavien Aké, Lana Childs, Jennifer Loo Farrar, C A Patrick Gbaguidi, Frédéric Kambou, Reggis Katsande, Miwako Kobayashi, Anderson Latt, Clement Lingani, Henju Marjuki, Lesley McGee, John Neatherlin, Ryan T Novak, Mahamoudou Ouattara, Lorenzo Pezzoli, Heidi M Soeters, Issa Tonde, Mamadou Tamboura, Zaneidou Mamane, Issaka Yameogo, Lucy A McNamara
Background Burkina Faso and Niger experience hyperendemic meningitis. We describe their bacterial meningitis epidemiology during 2015–2023, after meningococcal A and prior to meningococcal ACWYX (Men5CV) conjugate vaccine introductions. Methods Case-based surveillance included demographics, clinical information, and cerebrospinal fluid (CSF) specimens from suspected meningitis cases. CSFs were tested by real-time polymerase chain reaction (rt-PCR) and culture to detect Neisseria meningitidis (Nm), Streptococcus pneumoniae (Sp), or Haemophilus influenzae (Hi). Nm serogroup (A, C, W, Y, X, B or indeterminate) was established by rt-PCR or slide agglutination. Annual incidences were calculated using country census estimates as population denominators. Results During 2015–2023, 20,538 suspect cases were reported in Burkina Faso and 18,047 in Niger. In Burkina Faso, 3,722/16,350 CSF specimens tested were positive; 2,357 (64%) were Sp and 512 (14%) Nm serogroup W; Hi and Nm serogroups A, C, X, and indeterminate were also detected (<1–9% each). In Niger, 4,372/11,076 CSF specimens tested were positive; 3,003 (69%) were Nm serogroup C and 703 (16%) Sp; Hi and Nm serogroups B, W, X, and indeterminate were also detected (<1–8% each). Average annual incidences per 100,000 population of Nm, Sp, and Hi were 0.7, 1.6, and 0.2 for Burkina Faso and 4.1, 0.8, and 0.2 for Niger. Children ages 5-9 years in Burkina Faso and 10-14 years in Niger had the highest Nm incidences. Conclusions Nm, Sp and Hi continue to cause disease in Burkina Faso and Niger. Men5CV could help address the burden of serogroup C, W, and X meningococcal disease.
{"title":"Bacterial Meningitis Epidemiology in Burkina Faso and Niger - High-Risk Countries in the Meningitis Belt of Sub-Saharan Africa, 2015-2023","authors":"Veronica A Pinell-McNamara, Hamed S Ouédraogo, Lassane Kafando, Ousmane Sani, Aichatou Arzika Issoufou, Elhadji Ibrahim Tassiou, Mahamoudou Sanou, Felix Tarbangdo, Andre Bita, Katya Fernandez, Joann Kekeisen-Chen, Natacha Cureau, Adakal Aboubacar, Frédérick Acho, Flavien Aké, Lana Childs, Jennifer Loo Farrar, C A Patrick Gbaguidi, Frédéric Kambou, Reggis Katsande, Miwako Kobayashi, Anderson Latt, Clement Lingani, Henju Marjuki, Lesley McGee, John Neatherlin, Ryan T Novak, Mahamoudou Ouattara, Lorenzo Pezzoli, Heidi M Soeters, Issa Tonde, Mamadou Tamboura, Zaneidou Mamane, Issaka Yameogo, Lucy A McNamara","doi":"10.1093/infdis/jiag116","DOIUrl":"https://doi.org/10.1093/infdis/jiag116","url":null,"abstract":"Background Burkina Faso and Niger experience hyperendemic meningitis. We describe their bacterial meningitis epidemiology during 2015–2023, after meningococcal A and prior to meningococcal ACWYX (Men5CV) conjugate vaccine introductions. Methods Case-based surveillance included demographics, clinical information, and cerebrospinal fluid (CSF) specimens from suspected meningitis cases. CSFs were tested by real-time polymerase chain reaction (rt-PCR) and culture to detect Neisseria meningitidis (Nm), Streptococcus pneumoniae (Sp), or Haemophilus influenzae (Hi). Nm serogroup (A, C, W, Y, X, B or indeterminate) was established by rt-PCR or slide agglutination. Annual incidences were calculated using country census estimates as population denominators. Results During 2015–2023, 20,538 suspect cases were reported in Burkina Faso and 18,047 in Niger. In Burkina Faso, 3,722/16,350 CSF specimens tested were positive; 2,357 (64%) were Sp and 512 (14%) Nm serogroup W; Hi and Nm serogroups A, C, X, and indeterminate were also detected (&lt;1–9% each). In Niger, 4,372/11,076 CSF specimens tested were positive; 3,003 (69%) were Nm serogroup C and 703 (16%) Sp; Hi and Nm serogroups B, W, X, and indeterminate were also detected (&lt;1–8% each). Average annual incidences per 100,000 population of Nm, Sp, and Hi were 0.7, 1.6, and 0.2 for Burkina Faso and 4.1, 0.8, and 0.2 for Niger. Children ages 5-9 years in Burkina Faso and 10-14 years in Niger had the highest Nm incidences. Conclusions Nm, Sp and Hi continue to cause disease in Burkina Faso and Niger. Men5CV could help address the burden of serogroup C, W, and X meningococcal disease.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147278867","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}
Moments of challenge can create opportunities for recognition, connection, and collective care. While we cannot always remove the sources of pain, we can meaningfully shape how they are experienced by ensuring that no one carries them alone. Guided by the idea that presence and validation are powerful forms of support, this exchange seeks to foster mutual recognition and affirm experiences that are too often minimized or overlooked. By creating space for shared acknowledgment and listening, it emphasizes solidarity over isolation and connection over silence. If this dialogue helps individuals feel seen, supported, and less alone, it affirms the enduring power of community and shared humanity.
{"title":"Holding One Another in a Time of Loss and Uncertainty","authors":"Sara Gianella","doi":"10.1093/infdis/jiag110","DOIUrl":"https://doi.org/10.1093/infdis/jiag110","url":null,"abstract":"Moments of challenge can create opportunities for recognition, connection, and collective care. While we cannot always remove the sources of pain, we can meaningfully shape how they are experienced by ensuring that no one carries them alone. Guided by the idea that presence and validation are powerful forms of support, this exchange seeks to foster mutual recognition and affirm experiences that are too often minimized or overlooked. By creating space for shared acknowledgment and listening, it emphasizes solidarity over isolation and connection over silence. If this dialogue helps individuals feel seen, supported, and less alone, it affirms the enduring power of community and shared humanity.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"80 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146778461","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}
Humphrey Mulenga, Simon C Mendelsohn, Andrew Fiore-Gartland, Adam Penn-Nicholson, Munyaradzi Musvosvi, Michèle Tameris, Gerhard Walzl, Kogieleum Naidoo, Gavin Churchyard, Thomas J Scriba, Mark Hatherill
Background Identifying risk factors for Mtb sensitization (defined as IGRA-positive) and progression to TB disease is critical to guide targeted prevention strategies. Methods We analyzed data from a prospective cohort of adults (18–60 years) without HIV, enrolled at five high-incidence South African sites. Participants underwent testing for Mtb sensitization and microbiologically-confirmed TB at baseline, and during 15 months follow-up. Multivariable logistic and Cox regression models were used to assess factors associated with Mtb sensitization and TB progression. Sampling weights were applied to reflect the screened population. Results Among 2,912 participants with valid IGRA results, 63.4% (n=1895) were Mtb-sensitized. Prevalent TB was detected in 1.81% (62/1895) of Mtb-sensitized versus 0.62% (12/1017) of Mtb-unsensitized individuals (p=0.01). During follow-up of participants without prevalent TB, 2.01% (48/1833) Mtb-sensitized and 0.53% (8/1005) Mtb-unsensitized individuals developed TB (p=0.01). Factors associated with Mtb sensitization included increasing age (adjusted-odds-ratio; aOR=1.02 , 95%CI 1.01–1.03), male sex (aOR=1.34, 95%CI 1.08–1.67), smoking (aOR=1.31, 95%CI 1.05–1.64), prior TB (aOR=2.20, 95%CI 1.40–3.47), and TB contact history (aOR=1.40, 95%CI 1.08–1.83). Risk factors for progression to TB were Mtb sensitization (adjusted-hazard-ratio; aHR=3.05, 95%CI 1.14–8.18), smoking history (aHR=2.34, 95%CI 1.03–5.31), and lower body-mass index (aHR=0.89, 95%CI 0.82–0.97). Conclusion Mtb-sensitized individuals had a three-fold higher risk of prevalent TB and progressing to TB compared to Mtb-unsensitized individuals. In high-prevalence settings, identifying individuals at greatest risk—such as those recently infected, with a history of smoking, or low BMI—could help refine TB prevention efforts and reduce community-level transmission.
{"title":"Risk factors for immunological sensitization to Mycobacterium tuberculosi s and progression to incident TB disease among HIV-uninfected adults in a high burden setting","authors":"Humphrey Mulenga, Simon C Mendelsohn, Andrew Fiore-Gartland, Adam Penn-Nicholson, Munyaradzi Musvosvi, Michèle Tameris, Gerhard Walzl, Kogieleum Naidoo, Gavin Churchyard, Thomas J Scriba, Mark Hatherill","doi":"10.1093/infdis/jiag100","DOIUrl":"https://doi.org/10.1093/infdis/jiag100","url":null,"abstract":"Background Identifying risk factors for Mtb sensitization (defined as IGRA-positive) and progression to TB disease is critical to guide targeted prevention strategies. Methods We analyzed data from a prospective cohort of adults (18–60 years) without HIV, enrolled at five high-incidence South African sites. Participants underwent testing for Mtb sensitization and microbiologically-confirmed TB at baseline, and during 15 months follow-up. Multivariable logistic and Cox regression models were used to assess factors associated with Mtb sensitization and TB progression. Sampling weights were applied to reflect the screened population. Results Among 2,912 participants with valid IGRA results, 63.4% (n=1895) were Mtb-sensitized. Prevalent TB was detected in 1.81% (62/1895) of Mtb-sensitized versus 0.62% (12/1017) of Mtb-unsensitized individuals (p=0.01). During follow-up of participants without prevalent TB, 2.01% (48/1833) Mtb-sensitized and 0.53% (8/1005) Mtb-unsensitized individuals developed TB (p=0.01). Factors associated with Mtb sensitization included increasing age (adjusted-odds-ratio; aOR=1.02 , 95%CI 1.01–1.03), male sex (aOR=1.34, 95%CI 1.08–1.67), smoking (aOR=1.31, 95%CI 1.05–1.64), prior TB (aOR=2.20, 95%CI 1.40–3.47), and TB contact history (aOR=1.40, 95%CI 1.08–1.83). Risk factors for progression to TB were Mtb sensitization (adjusted-hazard-ratio; aHR=3.05, 95%CI 1.14–8.18), smoking history (aHR=2.34, 95%CI 1.03–5.31), and lower body-mass index (aHR=0.89, 95%CI 0.82–0.97). Conclusion Mtb-sensitized individuals had a three-fold higher risk of prevalent TB and progressing to TB compared to Mtb-unsensitized individuals. In high-prevalence settings, identifying individuals at greatest risk—such as those recently infected, with a history of smoking, or low BMI—could help refine TB prevention efforts and reduce community-level transmission.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215630","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}
Ronnie Ndizeye, Annika K Gunderson, Emmanuel Baguma, Dana A Giandomenico, Moses Ntaro, Edgar M Mulogo, Ross M Boyce
We evaluated the diagnostic agreement of expired malaria rapid diagnostic tests (mRDTs) with non-expired mRDTs in a clinical setting in western Uganda. Expired mRDTs (SD Bioline Ag Pf/Pan and First Reponse Ag pLDH/HRP2) were administered to each participant in parallel with a non-expired mRDT serving as the reference. Of 200 participants, 21 (10.5%) tested positive and 179 (89.5%) tested negative for malaria. All tests up to 9-months post-expiration were valid and consistent with reference mRDTs. All mRDTs 10- to 12-months post-expiration were invalid. These preliminary findings support further research into the use of expired mRDTs in resource limited settings.
我们在乌干达西部的一个临床环境中评估了过期的疟疾快速诊断试验（mRDTs）与未过期的mRDTs的诊断一致性。每个参与者同时服用过期的mRDT (SD Bioline Ag Pf/Pan和First response Ag pLDH/HRP2)，并以未过期的mRDT作为参考。在200名参与者中，21人（10.5%）疟疾检测呈阳性，179人（89.5%）疟疾检测呈阴性。有效期后9个月的所有检测均有效，且与参考mrdt一致。所有有效期后10至12个月的mrdt均无效。这些初步发现支持进一步研究在资源有限的情况下使用过期的mrdt。
{"title":"Test Performance of Expired Malaria Rapid Diagnostic Tests: A pilot diagnostic accuracy study conducted in Western Uganda","authors":"Ronnie Ndizeye, Annika K Gunderson, Emmanuel Baguma, Dana A Giandomenico, Moses Ntaro, Edgar M Mulogo, Ross M Boyce","doi":"10.1093/infdis/jiag105","DOIUrl":"https://doi.org/10.1093/infdis/jiag105","url":null,"abstract":"We evaluated the diagnostic agreement of expired malaria rapid diagnostic tests (mRDTs) with non-expired mRDTs in a clinical setting in western Uganda. Expired mRDTs (SD Bioline Ag Pf/Pan and First Reponse Ag pLDH/HRP2) were administered to each participant in parallel with a non-expired mRDT serving as the reference. Of 200 participants, 21 (10.5%) tested positive and 179 (89.5%) tested negative for malaria. All tests up to 9-months post-expiration were valid and consistent with reference mRDTs. All mRDTs 10- to 12-months post-expiration were invalid. These preliminary findings support further research into the use of expired mRDTs in resource limited settings.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222859","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}
Rajiv S Jumani, Bryanna Thomas, Jay Lakshman, Christian Ostermeier, Natko Nuber, Juergen Hubert Blusch, Sofia Braud-Perez, Dean Wetty, Lizhuo Nouaime, Juergen Dederichs, Joseph Etse, Slobodan Grubesic, Suresh B Lakshminarayana, Lucy C Watson, Johanne Blais, Zachary Thompson, Tareq Z Jaber, Mark R Jones, Deborah A Schaefer, Michael W Riggs, Christopher D Huston, Thierry T Diagana, Ujjini H Manjunatha
Background Cryptosporidiosis is a leading cause of severe diarrhea and mortality in young children with no vaccine or effective treatment. Cryptosporidium controlled human infection model (CHIM) in healthy adults provides an opportunity to evaluate the safety and efficacy of novel chemical entities prior to testing in young pediatric patients. However, CHIM development has been hindered by the lack of current good manufacturing practice (cGMP)-compliant Cryptosporidium parvum oocysts, which are required for filing an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration. Methods To overcome this barrier, we developed a cGMP-compliant process for producing C. parvum oocysts. The approach involved sourcing well-characterized oocysts purified from neonatal calves under controlled non-GMP conditions, followed by cGMP processing that included peracetic acid–based surface sanitization, comprehensive microbial testing and release as a non-sterile oral product for human use. Results Peracetic acid (0.5% for 20 minutes) treated C. parvum oocysts demonstrated acceptable microbial safety and preserved viability. Viability was assessed through oocyst excystation, HCT-8 cell infection and mouse infectivity studies. The cGMP produced C. parvum oocysts with stringent batch-release test criteria for quantity, purity, identity, potency and bioburden was released as ABO809 for clinical use under an IND. ABO809 was successfully used in human challenge studies, producing reliable infection and characteristic clinical symptoms in healthy adult volunteers. Conclusions We describe a robust cGMP-compliant and qualification process for C. parvum oocysts that enables CHIM studies in healthy adults. Thereby opening avenues to evaluate efficacy of novel therapeutics and vaccines to treat cryptosporidiosis.
{"title":"Development of a current Good Manufacturing Practice-compliant Process for Producing Cryptosporidium parvum oocysts for Clinical Use","authors":"Rajiv S Jumani, Bryanna Thomas, Jay Lakshman, Christian Ostermeier, Natko Nuber, Juergen Hubert Blusch, Sofia Braud-Perez, Dean Wetty, Lizhuo Nouaime, Juergen Dederichs, Joseph Etse, Slobodan Grubesic, Suresh B Lakshminarayana, Lucy C Watson, Johanne Blais, Zachary Thompson, Tareq Z Jaber, Mark R Jones, Deborah A Schaefer, Michael W Riggs, Christopher D Huston, Thierry T Diagana, Ujjini H Manjunatha","doi":"10.1093/infdis/jiag107","DOIUrl":"https://doi.org/10.1093/infdis/jiag107","url":null,"abstract":"Background Cryptosporidiosis is a leading cause of severe diarrhea and mortality in young children with no vaccine or effective treatment. Cryptosporidium controlled human infection model (CHIM) in healthy adults provides an opportunity to evaluate the safety and efficacy of novel chemical entities prior to testing in young pediatric patients. However, CHIM development has been hindered by the lack of current good manufacturing practice (cGMP)-compliant Cryptosporidium parvum oocysts, which are required for filing an Investigational New Drug Application (IND) with the U.S. Food and Drug Administration. Methods To overcome this barrier, we developed a cGMP-compliant process for producing C. parvum oocysts. The approach involved sourcing well-characterized oocysts purified from neonatal calves under controlled non-GMP conditions, followed by cGMP processing that included peracetic acid–based surface sanitization, comprehensive microbial testing and release as a non-sterile oral product for human use. Results Peracetic acid (0.5% for 20 minutes) treated C. parvum oocysts demonstrated acceptable microbial safety and preserved viability. Viability was assessed through oocyst excystation, HCT-8 cell infection and mouse infectivity studies. The cGMP produced C. parvum oocysts with stringent batch-release test criteria for quantity, purity, identity, potency and bioburden was released as ABO809 for clinical use under an IND. ABO809 was successfully used in human challenge studies, producing reliable infection and characteristic clinical symptoms in healthy adult volunteers. Conclusions We describe a robust cGMP-compliant and qualification process for C. parvum oocysts that enables CHIM studies in healthy adults. Thereby opening avenues to evaluate efficacy of novel therapeutics and vaccines to treat cryptosporidiosis.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"132 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215649","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}
Giuseppe Sangiorgio, Grace Chamberlin, Riccardo Castagnoli, Brianna Wachter, Kerry A Dobbs, Danielle Fink, Gina A Montealegre Sanchez, Karyl Barron, Helen C Su, Douglas Kuhns, Peter D Burbelo, Luigi D Notarangelo, Esther Freeman, Ottavia M Delmonte
Most pandemic-associated chilblains (PAC) resolve spontaneously, but a subset of patients develops persistent or recurrent disease. We analyzed peripheral cytokine profiles in 17 patients with prolonged PAC and identified elevated IFN-γ, CXCL10, CX3CL1, IL-16, CCL22, and S100A8. In contrast to the transient type I interferon response described in acute PAC, prolonged disease was characterized by a type II interferon–skewed inflammatory signature with T cell activation and endothelial involvement. Frequent autoimmune comorbidities suggest baseline immune dysregulation contributing to chronicity. These findings highlight potential therapeutic targets, including JAK inhibition and IFN-γ–directed therapies.
{"title":"Immune-Based Cytokine Signatures of Prolonged Pandemic-Associated Chilblains","authors":"Giuseppe Sangiorgio, Grace Chamberlin, Riccardo Castagnoli, Brianna Wachter, Kerry A Dobbs, Danielle Fink, Gina A Montealegre Sanchez, Karyl Barron, Helen C Su, Douglas Kuhns, Peter D Burbelo, Luigi D Notarangelo, Esther Freeman, Ottavia M Delmonte","doi":"10.1093/infdis/jiag103","DOIUrl":"https://doi.org/10.1093/infdis/jiag103","url":null,"abstract":"Most pandemic-associated chilblains (PAC) resolve spontaneously, but a subset of patients develops persistent or recurrent disease. We analyzed peripheral cytokine profiles in 17 patients with prolonged PAC and identified elevated IFN-γ, CXCL10, CX3CL1, IL-16, CCL22, and S100A8. In contrast to the transient type I interferon response described in acute PAC, prolonged disease was characterized by a type II interferon–skewed inflammatory signature with T cell activation and endothelial involvement. Frequent autoimmune comorbidities suggest baseline immune dysregulation contributing to chronicity. These findings highlight potential therapeutic targets, including JAK inhibition and IFN-γ–directed therapies.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146222868","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}
Julien Gras, Marie Laure Nere, Julien Robert, Kevin Louis, Marie Noëlle Peraldi, Linda Feghoul, Jérôme Verine, Ali Amara, Carmen Lefaucheur, Jean Michel Molina, Constance Delaugerre, Maud Salmona
Background Among kidney transplant recipients (KTR) with BKPyV associated nephropathy (BKPyVN), the dynamics of BKPyV replication are not well established. We aim to investigate BKPyV genetic diversity and evolution following kidney transplantation. Methods We retrospectively analyzed 32 KTR with a biopsy-proven diagnosis of BKPyVN. Stored plasma and kidney biopsies were tested for BKPyV viral load, and BKPyV whole genome sequencing (WGS) performed on BKPyV-positive samples. Results A total of 104 samples positive for BKPyV DNA detection were sequenced, among which 83 were included in the analysis. BKPyV-I was the most frequent genotype detected, followed by BKPyV-IVc2 and BKPyV-II. At BKPyVN diagnosis (median time: 12 [8-17] months post-transplant), WGS identified the same BKPyV-subtype in the plasma and kidney biopsy for all patients but one. Alignment of BKPyV consensus sequences between the two compartments at the time of BKPyVN showed similarity > 99%, but identified single nucleotide polymorphisms in 13/23 of the cases, including 25% APOBEC-associated mutations. Among the 16 KTR with ≥ 2 consecutive BKPyV-positive samples available for analysis, consensus sequence showed a different BKPyV subtype in pre-BKPyVN kidney biopsies compared to BKPyVN in 9 patients. Before BKPyVN diagnosis, minority variants on VP1 sequence were identified in 10/11 kidney biopsy and 5/10 plasma samples. Conclusions Among KTR with BKPyVN, we show that BKPyV viral populations change over time, with the coexistence of several viral populations in early samples compared to BKPyVN, as a result of both APOBEC-mediated editing and replication-driven diversification within the kidney allograft.
{"title":"BK Polyomavirus Genetic Diversity and Evolution in Kidney Transplant Recipients with Viral Nephropathy Using Whole Genome Sequencing","authors":"Julien Gras, Marie Laure Nere, Julien Robert, Kevin Louis, Marie Noëlle Peraldi, Linda Feghoul, Jérôme Verine, Ali Amara, Carmen Lefaucheur, Jean Michel Molina, Constance Delaugerre, Maud Salmona","doi":"10.1093/infdis/jiag108","DOIUrl":"https://doi.org/10.1093/infdis/jiag108","url":null,"abstract":"Background Among kidney transplant recipients (KTR) with BKPyV associated nephropathy (BKPyVN), the dynamics of BKPyV replication are not well established. We aim to investigate BKPyV genetic diversity and evolution following kidney transplantation. Methods We retrospectively analyzed 32 KTR with a biopsy-proven diagnosis of BKPyVN. Stored plasma and kidney biopsies were tested for BKPyV viral load, and BKPyV whole genome sequencing (WGS) performed on BKPyV-positive samples. Results A total of 104 samples positive for BKPyV DNA detection were sequenced, among which 83 were included in the analysis. BKPyV-I was the most frequent genotype detected, followed by BKPyV-IVc2 and BKPyV-II. At BKPyVN diagnosis (median time: 12 [8-17] months post-transplant), WGS identified the same BKPyV-subtype in the plasma and kidney biopsy for all patients but one. Alignment of BKPyV consensus sequences between the two compartments at the time of BKPyVN showed similarity &gt; 99%, but identified single nucleotide polymorphisms in 13/23 of the cases, including 25% APOBEC-associated mutations. Among the 16 KTR with ≥ 2 consecutive BKPyV-positive samples available for analysis, consensus sequence showed a different BKPyV subtype in pre-BKPyVN kidney biopsies compared to BKPyVN in 9 patients. Before BKPyVN diagnosis, minority variants on VP1 sequence were identified in 10/11 kidney biopsy and 5/10 plasma samples. Conclusions Among KTR with BKPyVN, we show that BKPyV viral populations change over time, with the coexistence of several viral populations in early samples compared to BKPyVN, as a result of both APOBEC-mediated editing and replication-driven diversification within the kidney allograft.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215631","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}
Andrew P Platt, Viviane Callier, Alison Grazioli, Zonghui Hu, Sydney R Stein, Megan G Anders, Seth Warner, Emily Ricotta, Trevor M Stantliff, Jocelyn Wu, Nicole Hays, Katherine Raja, Ryan Curto, Madeleine Purcell, Shreya Singireddy, Douglas Tran, Raymond Rector, Sabrina Cho, Katelyn Wagner, Sabrina C Ramelli, Marcos J Ramos-Benitez, James Dickey, Jeffrey R Strich, Kevin M Vannella, Miranda Gibbons, Peter Rock, Ali Tabatabai, Michael T McCurdy, Thomas Scalea, Robert Christenson, Mohammad M Sajadi, Daniel Herr, Bradley Taylor, Kapil Saharia, Ronson J Madathil, Joseph Rabin, Dean Follmann, Daniel S Chertow
Background Critical illness in COVID-19 may require support with Extracorporeal Membrane Oxygenation (ECMO). As immunothrombosis contributes to pathogenesis of critical illness we quantified immunothrombotic markers in patients with COVID-19 on ECMO and evaluated the predictive capacity of these markers for death. Methods We performed a retrospective analysis of 74 consecutive patients with COVID-19 on ECMO at a single academic medical center between March 2020 and February 2021. SARS-CoV-2 nucleocapsid RNA and 16 immunothrombotic biomarkers were longitudinally quantified. Biomarker trajectories were assessed with univariate and multivariate models and used to predict death and decannulation across multiple models. Results Male sex, smoking status, high serum bilirubin level, and low partial pressure of oxygen in arterial blood to the fraction of inspired oxygen (P/F) ratio were associated with an increased risk of death. Plasma levels of 10 immunothrombotic markers were significantly elevated in fatal cases. Elevated IL-8 and von Willebrand factor (VWF) were associated with an increased hazard of death and elevated angiopoietin-2, IL-1β, IL-6, IL-8, IL-18, ICAM, p-selectin, syndecan-1, and VWF were associated with a decreased hazard for decannulation when adjusting for sex, smoking status, and time to cannulation. Predictive models incorporating biomarkers were superior to demographics alone and equivalent to models including clinical information. Conclusions We found increased immunothrombotic markers, male sex, and history of smoking were risk factors in patients with COVID-19 on ECMO who died as compared to those who were decannulated. These findings are important for understanding the pathogenesis of severe COVID-19 and prognostication.
{"title":"Plasma biomarkers of immunothrombosis are independently associated with death in patients with COVID-19 on ECMO","authors":"Andrew P Platt, Viviane Callier, Alison Grazioli, Zonghui Hu, Sydney R Stein, Megan G Anders, Seth Warner, Emily Ricotta, Trevor M Stantliff, Jocelyn Wu, Nicole Hays, Katherine Raja, Ryan Curto, Madeleine Purcell, Shreya Singireddy, Douglas Tran, Raymond Rector, Sabrina Cho, Katelyn Wagner, Sabrina C Ramelli, Marcos J Ramos-Benitez, James Dickey, Jeffrey R Strich, Kevin M Vannella, Miranda Gibbons, Peter Rock, Ali Tabatabai, Michael T McCurdy, Thomas Scalea, Robert Christenson, Mohammad M Sajadi, Daniel Herr, Bradley Taylor, Kapil Saharia, Ronson J Madathil, Joseph Rabin, Dean Follmann, Daniel S Chertow","doi":"10.1093/infdis/jiag106","DOIUrl":"https://doi.org/10.1093/infdis/jiag106","url":null,"abstract":"Background Critical illness in COVID-19 may require support with Extracorporeal Membrane Oxygenation (ECMO). As immunothrombosis contributes to pathogenesis of critical illness we quantified immunothrombotic markers in patients with COVID-19 on ECMO and evaluated the predictive capacity of these markers for death. Methods We performed a retrospective analysis of 74 consecutive patients with COVID-19 on ECMO at a single academic medical center between March 2020 and February 2021. SARS-CoV-2 nucleocapsid RNA and 16 immunothrombotic biomarkers were longitudinally quantified. Biomarker trajectories were assessed with univariate and multivariate models and used to predict death and decannulation across multiple models. Results Male sex, smoking status, high serum bilirubin level, and low partial pressure of oxygen in arterial blood to the fraction of inspired oxygen (P/F) ratio were associated with an increased risk of death. Plasma levels of 10 immunothrombotic markers were significantly elevated in fatal cases. Elevated IL-8 and von Willebrand factor (VWF) were associated with an increased hazard of death and elevated angiopoietin-2, IL-1β, IL-6, IL-8, IL-18, ICAM, p-selectin, syndecan-1, and VWF were associated with a decreased hazard for decannulation when adjusting for sex, smoking status, and time to cannulation. Predictive models incorporating biomarkers were superior to demographics alone and equivalent to models including clinical information. Conclusions We found increased immunothrombotic markers, male sex, and history of smoking were risk factors in patients with COVID-19 on ECMO who died as compared to those who were decannulated. These findings are important for understanding the pathogenesis of severe COVID-19 and prognostication.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"41 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146215668","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}
Kiran Bosco, Aleksandra Petrovic Fabijan, Jonathan Iredell, Krystyna Dabrowska, Ameneh Khatami
This review explores mammalian immune responses to phages with a particular emphasis on human immune responses to therapeutic phages and their potential implications for the outcomes of phage therapy. Despite the ubiquity of phages in the human microbiome, particularly in the gut (the phageome), research on immunological mechanisms governing immune responses to both endogenous and therapeutic phages are still in their infancy. We highlight key components of the immune system that contribute to clearance of phages in vivo and examine how various factors– including patient-specific variables, treatment regimens and phage characteristics can influence immune responses and, consequently, phage pharmacokinetics during therapy. A clearer understanding of human immune responses to phages is urgently needed to inform the development of more targeted and effective personalised phage therapies – an essential step in combating the escalating threat of antimicrobial resistance.
{"title":"Immune responses to phage therapy in humans: A review","authors":"Kiran Bosco, Aleksandra Petrovic Fabijan, Jonathan Iredell, Krystyna Dabrowska, Ameneh Khatami","doi":"10.1093/infdis/jiag096","DOIUrl":"https://doi.org/10.1093/infdis/jiag096","url":null,"abstract":"This review explores mammalian immune responses to phages with a particular emphasis on human immune responses to therapeutic phages and their potential implications for the outcomes of phage therapy. Despite the ubiquity of phages in the human microbiome, particularly in the gut (the phageome), research on immunological mechanisms governing immune responses to both endogenous and therapeutic phages are still in their infancy. We highlight key components of the immune system that contribute to clearance of phages in vivo and examine how various factors– including patient-specific variables, treatment regimens and phage characteristics can influence immune responses and, consequently, phage pharmacokinetics during therapy. A clearer understanding of human immune responses to phages is urgently needed to inform the development of more targeted and effective personalised phage therapies – an essential step in combating the escalating threat of antimicrobial resistance.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"299 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146169721","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：