Natalia Makarova,Tyana Singletary,M Melissa Peet,Kristen Kelley,Ryan Johnson,Vivek Agrahari,Maria Mendoza,Yi Pan,Walid Heneine,Meredith R Clark,J Gerardo García-Lerma,Gustavo F Doncel,James M Smith
On-demand topical inserts for HIV prevention may be a good option for people who have a low frequency of sexual activity. We recently demonstrated in a preclinical macaque model that rectal application of inserts containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) conferred protection against SHIV infection (93% efficacy) when applied as pre-exposure prophylaxis (PrEP) 4 hours before SHIV exposure. Here, we show that the same inserts provide significant post-exposure protection (82.9% efficacy) when applied four hours after SHIV exposure. Our findings further support the ongoing clinical development of TAF/EVG inserts for on-demand HIV prevention.
{"title":"Partial post-exposure protection by topical inserts containing tenofovir alafenamide fumarate/elvitegravir in a macaque model of rectal SHIV infection.","authors":"Natalia Makarova,Tyana Singletary,M Melissa Peet,Kristen Kelley,Ryan Johnson,Vivek Agrahari,Maria Mendoza,Yi Pan,Walid Heneine,Meredith R Clark,J Gerardo García-Lerma,Gustavo F Doncel,James M Smith","doi":"10.1093/infdis/jiaf611","DOIUrl":"https://doi.org/10.1093/infdis/jiaf611","url":null,"abstract":"On-demand topical inserts for HIV prevention may be a good option for people who have a low frequency of sexual activity. We recently demonstrated in a preclinical macaque model that rectal application of inserts containing tenofovir alafenamide fumarate (TAF) and elvitegravir (EVG) conferred protection against SHIV infection (93% efficacy) when applied as pre-exposure prophylaxis (PrEP) 4 hours before SHIV exposure. Here, we show that the same inserts provide significant post-exposure protection (82.9% efficacy) when applied four hours after SHIV exposure. Our findings further support the ongoing clinical development of TAF/EVG inserts for on-demand HIV prevention.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145664294","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}
Kelsey M Sumner,Mark Katz,Avital Hirsch,Alon Peretz,David Greenberg,Emily T Martin,Rachel Truscon,Laura J Edwards,Lauren Grant,Emma K Noble,Gabriella Newes-Adeyi,Jacob Dreiher,Alicia Fry,Brendan Flannery,Eduardo Azziz-Baumgartner,Arnold S Monto,Min Z Levine,Mark Thompson,Ran Balicer,Ashley Fowlkes
BACKGROUNDAdult studies have shown that quadrivalent recombinant influenza vaccines (RIV4) induce a higher antibody response than quadrivalent egg-based inactivated influenza vaccines (IIV4).METHODSHealthcare personnel (HCP) from a 2018-19 cohort study that assessed IIV4 immunogenicity in Israel were recruited into a 2019-20 randomized trial of RIV4 and IIV4. 2018-19 low titer low responders (LTLRs) had pre-vaccination hemagglutination inhibition antibody titers ≤1:40 and <4-foldrise post-vaccination. We assessed whether RIV4 versus IIV4 receipt in the 2019-20 season improved response among 2018-19 LTLRs using logistic regression adjusted for employment hospital.RESULTSOf 228 HCP classified as 2018-19 LTLRs, 2019-20 RIV4 recipients were 3.6 (95% CI: 1.2-11.4) and 8.3 (95% CI: 3.0-26.3) times as likely to become a non-LTLR against influenza A(H1N1)pdm09 and cell-derived A(H3N2) vaccine components compared to IIV4 recipients.CONCLUSIONSRIV4 had improved immunogenicity against influenza A viruses among previously classified low vaccine responder HCP, highlighting how recombinant influenza vaccines could improve antibody responses against influenza A for HCP at risk for poor influenza antibody response.
{"title":"Improved immune response against influenza A viruses with receipt of a recombinant influenza vaccine in healthcare personnel with prior low antibody response to egg-based influenza vaccines, Israel, 2019-20.","authors":"Kelsey M Sumner,Mark Katz,Avital Hirsch,Alon Peretz,David Greenberg,Emily T Martin,Rachel Truscon,Laura J Edwards,Lauren Grant,Emma K Noble,Gabriella Newes-Adeyi,Jacob Dreiher,Alicia Fry,Brendan Flannery,Eduardo Azziz-Baumgartner,Arnold S Monto,Min Z Levine,Mark Thompson,Ran Balicer,Ashley Fowlkes","doi":"10.1093/infdis/jiaf605","DOIUrl":"https://doi.org/10.1093/infdis/jiaf605","url":null,"abstract":"BACKGROUNDAdult studies have shown that quadrivalent recombinant influenza vaccines (RIV4) induce a higher antibody response than quadrivalent egg-based inactivated influenza vaccines (IIV4).METHODSHealthcare personnel (HCP) from a 2018-19 cohort study that assessed IIV4 immunogenicity in Israel were recruited into a 2019-20 randomized trial of RIV4 and IIV4. 2018-19 low titer low responders (LTLRs) had pre-vaccination hemagglutination inhibition antibody titers ≤1:40 and <4-foldrise post-vaccination. We assessed whether RIV4 versus IIV4 receipt in the 2019-20 season improved response among 2018-19 LTLRs using logistic regression adjusted for employment hospital.RESULTSOf 228 HCP classified as 2018-19 LTLRs, 2019-20 RIV4 recipients were 3.6 (95% CI: 1.2-11.4) and 8.3 (95% CI: 3.0-26.3) times as likely to become a non-LTLR against influenza A(H1N1)pdm09 and cell-derived A(H3N2) vaccine components compared to IIV4 recipients.CONCLUSIONSRIV4 had improved immunogenicity against influenza A viruses among previously classified low vaccine responder HCP, highlighting how recombinant influenza vaccines could improve antibody responses against influenza A for HCP at risk for poor influenza antibody response.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145656861","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}
Sujata E Tewari,Risa Hoffman,Shahin Lockman,Clare F Flanagan,Karen A Webb,Stephanie Horsfall,Anesu Chimwaza,Caitlin M Dugdale,Judith Currier,Efison Dhodho,Anne M Neilan,Kenneth Masiye,Aadia Rana,Angela Mushavi,Florence Ebem,Kudakwashe C Takarinda,Sophie Desmonde,Kenneth A Freedberg,Andrea L Ciaranello
BACKGROUNDLong-acting antiretroviral therapy (LA-ART) may reduce adherence barriers for postpartum women with HIV (PPWH), reducing vertical transmission (VT) and improving pediatric life expectancy (pLE), but efficacy and drug costs are uncertain.METHODSUsing a microsimulation model, we simulated mother-infant dyads for two cohorts of PPWH engaged in care, receiving oral tenofovir/lamivudine/dolutegravir (TLD) in pregnancy, and facing adherence challenges in Zimbabwe: mothers without (NVS) and with (VS) viral suppression at delivery. We modeled two post-delivery strategies: standard of care (SOC: TLD continuation) or LA-ART (switching to LA-cabotegravir/rilpivirine [CAB/RPV]). Key inputs included: 6-month-postpartum viral suppression (LA-ART: NVS = 85%/VS = 90%; SOC: NVS = 63%/VS = 78%), ART costs/year (CAB/RPV=$144/TLD=$43.20), and VT risk (0.06%-0.89%/month, range by maternal RNA). Outcomes include VT, pLE, costs (maternal ART in breastfeeding plus pediatric HIV-related lifetime care), and incremental cost-effectiveness ratios (ICERs, $/year-of-life-saved [YLS]; cost-effective: ICER≤$800/YLS [0.5× Zimbabwe GDP].RESULTSLA-ART would reduce VT compared with SOC (NVS: from 7.49% to 6.58%/VS: from 4.17% to 3.80%), averting ∼160 infections/year in Zimbabwe. For NVS, LA-ART would improve pLE (SOC = 66.08y, LA-ART = 66.40y) at nearly equal cost (SOC = $764/child, LA-ART = $763/child); LA-ART would not be cost-effective if CAB/RPV cost >$228/year or 6-month suppression were <74%. For VS, LA-ART would lead to higher pLE and costs (67.52y, $555/child) than SOC (67.40y, $445/child), with ICER=$2449/YLS; LA-ART would become cost-effective if CAB/RPV cost ≤$84/year.CONCLUSIONSLA-ART for breastfeeding women experiencing adherence challenges could reduce infant infections. If efficacies and costs are confirmed, LA-ART for NVS women would improve outcomes and be minimally cost-saving; for VS women, LA-ART would be cost-effective in Zimbabwe at costs ≤$84/year.
{"title":"Long-Acting Antiretroviral Therapy for Breastfeeding Women With HIV Experiencing Barriers to Adherence in Zimbabwe: Modeling Clinical Impact and Cost-effectiveness.","authors":"Sujata E Tewari,Risa Hoffman,Shahin Lockman,Clare F Flanagan,Karen A Webb,Stephanie Horsfall,Anesu Chimwaza,Caitlin M Dugdale,Judith Currier,Efison Dhodho,Anne M Neilan,Kenneth Masiye,Aadia Rana,Angela Mushavi,Florence Ebem,Kudakwashe C Takarinda,Sophie Desmonde,Kenneth A Freedberg,Andrea L Ciaranello","doi":"10.1093/infdis/jiaf521","DOIUrl":"https://doi.org/10.1093/infdis/jiaf521","url":null,"abstract":"BACKGROUNDLong-acting antiretroviral therapy (LA-ART) may reduce adherence barriers for postpartum women with HIV (PPWH), reducing vertical transmission (VT) and improving pediatric life expectancy (pLE), but efficacy and drug costs are uncertain.METHODSUsing a microsimulation model, we simulated mother-infant dyads for two cohorts of PPWH engaged in care, receiving oral tenofovir/lamivudine/dolutegravir (TLD) in pregnancy, and facing adherence challenges in Zimbabwe: mothers without (NVS) and with (VS) viral suppression at delivery. We modeled two post-delivery strategies: standard of care (SOC: TLD continuation) or LA-ART (switching to LA-cabotegravir/rilpivirine [CAB/RPV]). Key inputs included: 6-month-postpartum viral suppression (LA-ART: NVS = 85%/VS = 90%; SOC: NVS = 63%/VS = 78%), ART costs/year (CAB/RPV=$144/TLD=$43.20), and VT risk (0.06%-0.89%/month, range by maternal RNA). Outcomes include VT, pLE, costs (maternal ART in breastfeeding plus pediatric HIV-related lifetime care), and incremental cost-effectiveness ratios (ICERs, $/year-of-life-saved [YLS]; cost-effective: ICER≤$800/YLS [0.5× Zimbabwe GDP].RESULTSLA-ART would reduce VT compared with SOC (NVS: from 7.49% to 6.58%/VS: from 4.17% to 3.80%), averting ∼160 infections/year in Zimbabwe. For NVS, LA-ART would improve pLE (SOC = 66.08y, LA-ART = 66.40y) at nearly equal cost (SOC = $764/child, LA-ART = $763/child); LA-ART would not be cost-effective if CAB/RPV cost >$228/year or 6-month suppression were <74%. For VS, LA-ART would lead to higher pLE and costs (67.52y, $555/child) than SOC (67.40y, $445/child), with ICER=$2449/YLS; LA-ART would become cost-effective if CAB/RPV cost ≤$84/year.CONCLUSIONSLA-ART for breastfeeding women experiencing adherence challenges could reduce infant infections. If efficacies and costs are confirmed, LA-ART for NVS women would improve outcomes and be minimally cost-saving; for VS women, LA-ART would be cost-effective in Zimbabwe at costs ≤$84/year.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"110 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145644887","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}
BACKGROUNDIndia is transitioning to the visceral leishmaniasis (VL) post-elimination phase where robust surveillance is critical to sustaining elimination. We conducted a targeted longitudinal study combining epidemiological, serological, and entomological data in endemic villages in Bihar and Jharkhand states to assess active VL transmission levels.METHODSOur investigation was conducted in the villages of Rahar Diyara, Bihar, and Murbhanga, Jharkhand, based on spatial distribution of recently reported VL cases. Samples were collected quarterly from December 2021 to September 2022 in Rahar Diyara, and April 2022 to May 2023 in Murbhanga, to determine seroprevalence against Leishmania rK39 antigen. Sand flies were collected bi-weekly in Rahar Diyara (February to December, 2022) and Murbhanga (April to December, 2022) from different microhabitats and analyzed by qPCR targeting Leishmania kDNA.RESULTSrK39 Leishmania seroprevalence ranged from 20% to 30% in both villages. Murbhanga, an outbreak village, exhibited higher antibody levels in 9-23% of subjects compared with the low incidence village, Rahar Diyara (3-6%), reflecting a higher intensity of transmission in Murbhanga. Despite implementation of indoor residual spraying, Leishmania-infected sand flies were found in both villages, with 1.4% (4/285) and 1.2% (5/431) positive pools in Rahar Diyara and Murbhanga, respectively. Infected sand fly pools were collected from diverse microhabitats, predominantly from vegetation in Rahar Diyara and cattle enclosures in Murbhanga, indicative of focal and distinct patterns of transmission.CONCLUSIONSLow-level Leishmania transmission persists in India highlighting criticality of continued surveillance. Combining epidemiological, serological, and entomological surveys improves rapid outbreak assessment and intervention, and enhances efficacy of surveillance to sustain VL elimination.
{"title":"High Seropositivity to rK39 and Capture of Leishmania-Infected Sand Flies in Bihar and Jharkhand Emphasize the Need for Post-Elimination Surveillance of Visceral Leishmaniasis in India.","authors":"Eva Iniguez,Khushbu Priyamvada,Pushkar Dubey,Joy Bindroo,Mohammad Shahnawaz,Asahar Alam,Shalini Singh,Avneesh Kumar,Gaurav Kumar,Pankaj Kumar,Shani Pandey,Patrick Huffcutt,Claudio Meneses,Debanjan Patra,Indranil Sukla,Asgar Ali,Prabhas Kumar Mishra,Bikas Sinha,Tanmay Mahapatra,Tiago Donatelli Serafim,Ashok Kumar,Birendra Kumar Singh,Jesus G Valenzuela,Allen Hightower,Sridhar Srikantiah,Sadhana Sharma,Caryn Bern,Shaden Kamhawi","doi":"10.1093/infdis/jiaf543","DOIUrl":"https://doi.org/10.1093/infdis/jiaf543","url":null,"abstract":"BACKGROUNDIndia is transitioning to the visceral leishmaniasis (VL) post-elimination phase where robust surveillance is critical to sustaining elimination. We conducted a targeted longitudinal study combining epidemiological, serological, and entomological data in endemic villages in Bihar and Jharkhand states to assess active VL transmission levels.METHODSOur investigation was conducted in the villages of Rahar Diyara, Bihar, and Murbhanga, Jharkhand, based on spatial distribution of recently reported VL cases. Samples were collected quarterly from December 2021 to September 2022 in Rahar Diyara, and April 2022 to May 2023 in Murbhanga, to determine seroprevalence against Leishmania rK39 antigen. Sand flies were collected bi-weekly in Rahar Diyara (February to December, 2022) and Murbhanga (April to December, 2022) from different microhabitats and analyzed by qPCR targeting Leishmania kDNA.RESULTSrK39 Leishmania seroprevalence ranged from 20% to 30% in both villages. Murbhanga, an outbreak village, exhibited higher antibody levels in 9-23% of subjects compared with the low incidence village, Rahar Diyara (3-6%), reflecting a higher intensity of transmission in Murbhanga. Despite implementation of indoor residual spraying, Leishmania-infected sand flies were found in both villages, with 1.4% (4/285) and 1.2% (5/431) positive pools in Rahar Diyara and Murbhanga, respectively. Infected sand fly pools were collected from diverse microhabitats, predominantly from vegetation in Rahar Diyara and cattle enclosures in Murbhanga, indicative of focal and distinct patterns of transmission.CONCLUSIONSLow-level Leishmania transmission persists in India highlighting criticality of continued surveillance. Combining epidemiological, serological, and entomological surveys improves rapid outbreak assessment and intervention, and enhances efficacy of surveillance to sustain VL elimination.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"245 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145645052","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}
Nico A F Janssen,Mariolina Bruno,Yvonne Berk,Monique H E Reijers,Agostinho Carvalho,Roger J M Brüggemann,Paul E Verweij,Intan M W Dewi,Frank L van de Veerdonk
BACKGROUNDChronic pulmonary aspergillosis (CPA) usually develops in patients with pre-existing lung damage. However, little is known about potential underlying immune defects that might predispose patients to developing this debilitating condition.METHODSWe performed immunological analyses in 21 patients with CPA and 14 healthy controls. Polymorphonuclear granulocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) were isolated from venous blood. We measured reactive oxygen species (ROS) production and Aspergillus fumigatus killing capacity in PMNs and cytokine production by PBMCs in response to multiple stimuli after 24 hours (TNF-α, IL-1β, IL-6 and IL-1RA) and 7 days (IFN-γ, IL-17 and IL-22) by enzyme-linked immunosorbent assay.RESULTSPatients demonstrated no defects in PMN ROS production and A. fumigatus killing capacity as compared to controls. PBMC production of TNF-α, IL-1β and IL-6 did not differ significantly between both groups in response to all but one stimulus. However, IL-1RA production was significantly higher in patients in response to several stimuli. Patients demonstrated deficient IFN-γ production in response to several stimuli and a decreased IL-17 response to phytohaemagglutinin.Co-stimulation with A. fumigatus and M. avium leads to a synergistic TNF-α response in healthy controls, but synergism was lost in patients with CPA.CONCLUSIONSThe impaired IFN-γ and (more restricted) IL-17 response found in patients with CPA indicate an adaptive immunity/lymphocyte defect. Patients produce higher concentrations of the anti-inflammatory cytokine IL-1RA and demonstrate loss of synergistic TNF-α production after co-stimulation with A. fumigatus and M. avium. No significant innate immune response defects were found in patients with CPA.
{"title":"Interferon-gamma production defects characterise immune responses in patients with chronic pulmonary aspergillosis.","authors":"Nico A F Janssen,Mariolina Bruno,Yvonne Berk,Monique H E Reijers,Agostinho Carvalho,Roger J M Brüggemann,Paul E Verweij,Intan M W Dewi,Frank L van de Veerdonk","doi":"10.1093/infdis/jiaf596","DOIUrl":"https://doi.org/10.1093/infdis/jiaf596","url":null,"abstract":"BACKGROUNDChronic pulmonary aspergillosis (CPA) usually develops in patients with pre-existing lung damage. However, little is known about potential underlying immune defects that might predispose patients to developing this debilitating condition.METHODSWe performed immunological analyses in 21 patients with CPA and 14 healthy controls. Polymorphonuclear granulocytes (PMNs) and peripheral blood mononuclear cells (PBMCs) were isolated from venous blood. We measured reactive oxygen species (ROS) production and Aspergillus fumigatus killing capacity in PMNs and cytokine production by PBMCs in response to multiple stimuli after 24 hours (TNF-α, IL-1β, IL-6 and IL-1RA) and 7 days (IFN-γ, IL-17 and IL-22) by enzyme-linked immunosorbent assay.RESULTSPatients demonstrated no defects in PMN ROS production and A. fumigatus killing capacity as compared to controls. PBMC production of TNF-α, IL-1β and IL-6 did not differ significantly between both groups in response to all but one stimulus. However, IL-1RA production was significantly higher in patients in response to several stimuli. Patients demonstrated deficient IFN-γ production in response to several stimuli and a decreased IL-17 response to phytohaemagglutinin.Co-stimulation with A. fumigatus and M. avium leads to a synergistic TNF-α response in healthy controls, but synergism was lost in patients with CPA.CONCLUSIONSThe impaired IFN-γ and (more restricted) IL-17 response found in patients with CPA indicate an adaptive immunity/lymphocyte defect. Patients produce higher concentrations of the anti-inflammatory cytokine IL-1RA and demonstrate loss of synergistic TNF-α production after co-stimulation with A. fumigatus and M. avium. No significant innate immune response defects were found in patients with CPA.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"200 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613388","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}
Caitlin A Cassidy,Bonnie E Shook-Sa,Ross M Boyce,Emily J Ciccone,Emily W Gower,Amber M Young,Jessie K Edwards
BACKGROUNDMalaria rapid diagnostic tests (mRDTs) are a cornerstone of malaria testing and treatment efforts globally. However, positive mRDT results can occur after treatment due to antigen persistence, even in the absence of malaria parasites. False-negative mRDTs are well-described, but less is known about the prevalence and consequences of such false-positive results.METHODSWe estimated the prevalence of false-positive mRDTs, defined as mRDT(+)/microscopy(-), using data from the 2018-19 Uganda Malaria Indicator Survey. Children aged <5 years (under-5s) with paired mRDT and microscopy results were included. We estimated the prevalence of false-positive mRDTs among microscopy(-) children using survey weights. We fit bivariate generalized linear models to estimate the prevalence difference (PD) of false-positive mRDTs for pre-specified covariates. We constructed cross-validated weighted lasso regression models to determine which variables best predict false-positive mRDTs among children with recent fever.RESULTSThe prevalence of false-positive mRDTs was 10.7% (849/6786) and was strongly correlated with region-level transmission intensity. Prevalence was higher among children with recent fever (PD: 17.2%; 95% CI: 13.7%, 20.6%), recent antimalarial use (14.7%; 7.1%, 22.3%), and comorbid anemia (8.1%; 5.9%, 10.3%). Prevalence was lower among those with recent antibiotic use (-17.6%; -22.5%, -12.7%). A model with clinical, environmental, and household variables better predicted false-positive mRDTs (weighted AUC = 0.79) than individual models.CONCLUSIONSFalse-positive mRDTs are prevalent among under-5s in the 2018-19 Uganda MIS and lead to overestimates of community-level malaria prevalence. These results suggest that false-positive mRDTs may also contribute to misdiagnosis and unnecessary antimalarial use in clinical settings.
{"title":"False-positive malaria rapid diagnostic tests are prevalent among children under 5 years of age in Uganda.","authors":"Caitlin A Cassidy,Bonnie E Shook-Sa,Ross M Boyce,Emily J Ciccone,Emily W Gower,Amber M Young,Jessie K Edwards","doi":"10.1093/infdis/jiaf604","DOIUrl":"https://doi.org/10.1093/infdis/jiaf604","url":null,"abstract":"BACKGROUNDMalaria rapid diagnostic tests (mRDTs) are a cornerstone of malaria testing and treatment efforts globally. However, positive mRDT results can occur after treatment due to antigen persistence, even in the absence of malaria parasites. False-negative mRDTs are well-described, but less is known about the prevalence and consequences of such false-positive results.METHODSWe estimated the prevalence of false-positive mRDTs, defined as mRDT(+)/microscopy(-), using data from the 2018-19 Uganda Malaria Indicator Survey. Children aged <5 years (under-5s) with paired mRDT and microscopy results were included. We estimated the prevalence of false-positive mRDTs among microscopy(-) children using survey weights. We fit bivariate generalized linear models to estimate the prevalence difference (PD) of false-positive mRDTs for pre-specified covariates. We constructed cross-validated weighted lasso regression models to determine which variables best predict false-positive mRDTs among children with recent fever.RESULTSThe prevalence of false-positive mRDTs was 10.7% (849/6786) and was strongly correlated with region-level transmission intensity. Prevalence was higher among children with recent fever (PD: 17.2%; 95% CI: 13.7%, 20.6%), recent antimalarial use (14.7%; 7.1%, 22.3%), and comorbid anemia (8.1%; 5.9%, 10.3%). Prevalence was lower among those with recent antibiotic use (-17.6%; -22.5%, -12.7%). A model with clinical, environmental, and household variables better predicted false-positive mRDTs (weighted AUC = 0.79) than individual models.CONCLUSIONSFalse-positive mRDTs are prevalent among under-5s in the 2018-19 Uganda MIS and lead to overestimates of community-level malaria prevalence. These results suggest that false-positive mRDTs may also contribute to misdiagnosis and unnecessary antimalarial use in clinical settings.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"196 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613197","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}
Patricia Winokur,Theresa E Hegmann,Hana M El Sahly,Evan J Anderson,
This study of a measles-vectored vaccine for chikungunya virus (MV-CHIK) was a Phase 1 randomized, double-blinded, placebo-controlled trial with varying intervals between the 2 doses. The 6 cohorts each had 30 subjects, of which 25 received MV-CHIK and 5 received placebo. The 5 × 105 TCID50 dose was superior to the 5 × 104 TCID50 dose, and longer dosing intervals resulted in higher titers in the high dose groups. Mild to moderate injection site and systemic reactogenicity was common but brief. There was no evidence of prolonged vaccine-related arthralgia.
{"title":"A Phase 1 Double-Blinded Trial to Evaluate Safety, Immunogenicity, and Dosing of Measles-Vectored Chikungunya Virus Vaccine (MV-CHIK) in Healthy Adults.","authors":"Patricia Winokur,Theresa E Hegmann,Hana M El Sahly,Evan J Anderson, ","doi":"10.1093/infdis/jiaf571","DOIUrl":"https://doi.org/10.1093/infdis/jiaf571","url":null,"abstract":"This study of a measles-vectored vaccine for chikungunya virus (MV-CHIK) was a Phase 1 randomized, double-blinded, placebo-controlled trial with varying intervals between the 2 doses. The 6 cohorts each had 30 subjects, of which 25 received MV-CHIK and 5 received placebo. The 5 × 105 TCID50 dose was superior to the 5 × 104 TCID50 dose, and longer dosing intervals resulted in higher titers in the high dose groups. Mild to moderate injection site and systemic reactogenicity was common but brief. There was no evidence of prolonged vaccine-related arthralgia.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"126 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145613334","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}
BACKGROUNDIn patients with colorectal cancer (CRC), intestinal dysbiosis has been observed, with abnormal colonization of the colonic mucosa by pathogenic Escherichia coli strains producing a cyclomodulin named cytotoxic necrotizing factor (CNF). Cyclomodulins are bacterial toxins capable of altering the cell cycle of the infected cell. One of the mechanisms involved in host defense against pathogens and in carcinogenesis is autophagy. Here, we aimed at investigating the role of autophagy in colorectal carcinogenesis in the context of CNF-producing E. coli, designated as CyPEC (cytotoxic necrotizing factor-producing E. coli), infection.METHODSApcMin/+ mice predisposed to CRC development with autophagy deficiency specifically in intestinal epithelial cells (ApcMin/+/Atg16l1ΔIEC) were infected with the clinical 21F8 strain or the mutant 21F8Δcnf1, which does not produce CNF1.RESULTSIn ApcMin/+ mice, infection with 21F8 or 21F8Δcnf1 did not have an impact on the number and the size of colonic tumors. However, in ApcMin/+/Atg16l1ΔIEC mice, infection with 21F8 increased number and size of colonic tumors, compared with uninfected or 21F8Δcnf1-infected condition. This increase was CNF1-dependent as it was not observed upon infection with the 21F8Δcnf1 mutant. Mechanistically, the increase in tumorigenesis in ApcMin/+/Atg16l1ΔIEC mice upon 21F8 infection was associated with enhanced proliferation and decreased apoptosis of colonic epithelial cells.CONCLUSIONSOur results show that autophagy deficiency could be a genetic susceptibility for the development of CRC in patients with abnormal colonization by CyPEC strains.
{"title":"Cytotoxic necrotizing factor 1-producing E. coli enhance colorectal tumorigenesis in ApcMin/+ mice with autophagy deficiency in intestinal epithelial cells.","authors":"Coline Desseux,Alison Da Silva,Anaëlle Tassini,Pierre Sauvanet,Julien Delmas,Guillaume Dalmasso,Hang Thi Thu Nguyen","doi":"10.1093/infdis/jiaf586","DOIUrl":"https://doi.org/10.1093/infdis/jiaf586","url":null,"abstract":"BACKGROUNDIn patients with colorectal cancer (CRC), intestinal dysbiosis has been observed, with abnormal colonization of the colonic mucosa by pathogenic Escherichia coli strains producing a cyclomodulin named cytotoxic necrotizing factor (CNF). Cyclomodulins are bacterial toxins capable of altering the cell cycle of the infected cell. One of the mechanisms involved in host defense against pathogens and in carcinogenesis is autophagy. Here, we aimed at investigating the role of autophagy in colorectal carcinogenesis in the context of CNF-producing E. coli, designated as CyPEC (cytotoxic necrotizing factor-producing E. coli), infection.METHODSApcMin/+ mice predisposed to CRC development with autophagy deficiency specifically in intestinal epithelial cells (ApcMin/+/Atg16l1ΔIEC) were infected with the clinical 21F8 strain or the mutant 21F8Δcnf1, which does not produce CNF1.RESULTSIn ApcMin/+ mice, infection with 21F8 or 21F8Δcnf1 did not have an impact on the number and the size of colonic tumors. However, in ApcMin/+/Atg16l1ΔIEC mice, infection with 21F8 increased number and size of colonic tumors, compared with uninfected or 21F8Δcnf1-infected condition. This increase was CNF1-dependent as it was not observed upon infection with the 21F8Δcnf1 mutant. Mechanistically, the increase in tumorigenesis in ApcMin/+/Atg16l1ΔIEC mice upon 21F8 infection was associated with enhanced proliferation and decreased apoptosis of colonic epithelial cells.CONCLUSIONSOur results show that autophagy deficiency could be a genetic susceptibility for the development of CRC in patients with abnormal colonization by CyPEC strains.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145600027","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}
Emma Faddy, Mikkel Illemann Johansen, Christoffer Gadeberg, Rikke Louise Meyer, Lars Østergaard, Cecilie Bay-Richter, Louise Kruse Jensen, Mikkel Holm Vendelbo, Nis Pedersen Jørgensen
Objectives Vascular graft or endograft infections (VGEI) pose a detrimental complication when using vascular grafts and are challenging to diagnose and treat. This study examined the progression of infection and the antimicrobial response in VGEI using [18F]Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET), ex vivo bacterial quantification, and histology in a VGEI rat model. Methods In this experimental study, 97 male Sprague-Dawley rats had a polytetrafluorethylene graft surgically implanted in the carotid artery. The graft was either pre-inoculated with Staphylococcus aureus, Staphylococcus epidermidis, or saline. Up to 31 days after surgery, rats were FDG-PET-scanned. Subsequently, they were euthanised, and the implants were retrieved for analysis. A subgroup of infected rats received daptomycin and rifampicin from days 20 to 29. Results Tracer uptake around the implant, measured by maximum standardised uptake value (SUVmax), declined over time in all groups. Between groups, SUVmax was highest in untreated S. aureus-infected rats. When comparing antibiotic-treated and uninfected rats by day 31, there was no difference in SUVmax, although the treated rats were still infected. Histology revealed widespread inflammation by day 10 in S. aureus-infected rats, which decreased by days 20 and 31 with encapsulation of the infection, alongside increased plasma interleukin-10. Conclusions FDG-PET differentiated untreated S. aureus-infected rats from uninfected ones but failed to monitor infection progression, as SUVmax declined over time despite a constant bacterial load. FDG-PET could not distinguish between uninfected rats and those with suppressed infection, likely due to reduced inflammation and encapsulation of the infection.
{"title":"[18F]Fluorodeoxyglucose Positron Emission Tomography for diagnosis and monitoring of acute Staphylococcus aureus vascular graft infection in a rat model","authors":"Emma Faddy, Mikkel Illemann Johansen, Christoffer Gadeberg, Rikke Louise Meyer, Lars Østergaard, Cecilie Bay-Richter, Louise Kruse Jensen, Mikkel Holm Vendelbo, Nis Pedersen Jørgensen","doi":"10.1093/infdis/jiaf594","DOIUrl":"https://doi.org/10.1093/infdis/jiaf594","url":null,"abstract":"Objectives Vascular graft or endograft infections (VGEI) pose a detrimental complication when using vascular grafts and are challenging to diagnose and treat. This study examined the progression of infection and the antimicrobial response in VGEI using [18F]Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET), ex vivo bacterial quantification, and histology in a VGEI rat model. Methods In this experimental study, 97 male Sprague-Dawley rats had a polytetrafluorethylene graft surgically implanted in the carotid artery. The graft was either pre-inoculated with Staphylococcus aureus, Staphylococcus epidermidis, or saline. Up to 31 days after surgery, rats were FDG-PET-scanned. Subsequently, they were euthanised, and the implants were retrieved for analysis. A subgroup of infected rats received daptomycin and rifampicin from days 20 to 29. Results Tracer uptake around the implant, measured by maximum standardised uptake value (SUVmax), declined over time in all groups. Between groups, SUVmax was highest in untreated S. aureus-infected rats. When comparing antibiotic-treated and uninfected rats by day 31, there was no difference in SUVmax, although the treated rats were still infected. Histology revealed widespread inflammation by day 10 in S. aureus-infected rats, which decreased by days 20 and 31 with encapsulation of the infection, alongside increased plasma interleukin-10. Conclusions FDG-PET differentiated untreated S. aureus-infected rats from uninfected ones but failed to monitor infection progression, as SUVmax declined over time despite a constant bacterial load. FDG-PET could not distinguish between uninfected rats and those with suppressed infection, likely due to reduced inflammation and encapsulation of the infection.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145608730","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}
Neraide Biai, Simon-Pierre Ndimbo-Kumugo, Severin Loul, Innocent Ndong Bass, Maëliss Champagne, Placide Mbala Kingebeni, Eric Delaporte, Jean-Jacques Muyembe-Tamfum, Charles Kouanfack, Ahidjo Ayouba, Steve Ahuka-Mundeke, Martine Peeters
Background The mpox outbreak in august 2024 in central Africa, together with the mpox pandemic in 2022 associated with the emergence of new viral lineages in urban areas highlighted that this historically neglected zoonotic tropical disease caused by mpox virus (MPXV) is of public health concern. The majority of mpox infections are of zoonotic origin, but knowledge on the animal reservoir of MPXV is still extremely limited. Methods Non-human primate (NHP) samples (n=1,571) from 29 different species, collected across Cameroon and the Democratic Republic of the Congo (DRC) were tested for the presence of IgG antibodies with a peptide-based multiplex mpox serological assay. Results According to stringent or less-stringent cut-off used, 17 to 85 animals (1.1-5.4%) had antibodies to at least one of the three peptides used. Seropositive samples were observed in seven to fifteen species, including Cercopithecus sp (C.ascanius, C.cephus, C.mitis, C.nictitans, C.neglectus, C.pogonias), Cercocebus sp (C.torquatus, C.agilis), Colobus sp (C.angolensis, C.guereza), Papio anubis, Lophocebus albigena, Mandrillus sphinx, Allenopithecus nigroviridis and Pan troglodytes. Mpox seroprevalence was higher in Cameroon than in DRC, i.e. 1.7-8.5% versus 0.2-0.9% (p<0.01 - p<0.001), respectively. Seroprevalence differed also according to sampling sites. In several sites, more than one NHP species was seropositive. Mpox seroprevalence differed, but not significantly in arboreal (1.2-5.4%; 15-69/1,267), semi-terrestrial (1.1-4.3%; 1-4/92) and terrestrial species (0.5-5.7%; 1-12/212). Conclusion The low overall seroprevalence suggests that NHPs are most likely intermediate hosts and may be infected by other species, including reservoirs. However, they remain a potential source of human infection.
{"title":"Serological survey in multiple African non-human primate species in Cameroon and the Democratic Republic of the Congo reveals low overall seroprevalence to mpox virus (MPXV)","authors":"Neraide Biai, Simon-Pierre Ndimbo-Kumugo, Severin Loul, Innocent Ndong Bass, Maëliss Champagne, Placide Mbala Kingebeni, Eric Delaporte, Jean-Jacques Muyembe-Tamfum, Charles Kouanfack, Ahidjo Ayouba, Steve Ahuka-Mundeke, Martine Peeters","doi":"10.1093/infdis/jiaf602","DOIUrl":"https://doi.org/10.1093/infdis/jiaf602","url":null,"abstract":"Background The mpox outbreak in august 2024 in central Africa, together with the mpox pandemic in 2022 associated with the emergence of new viral lineages in urban areas highlighted that this historically neglected zoonotic tropical disease caused by mpox virus (MPXV) is of public health concern. The majority of mpox infections are of zoonotic origin, but knowledge on the animal reservoir of MPXV is still extremely limited. Methods Non-human primate (NHP) samples (n=1,571) from 29 different species, collected across Cameroon and the Democratic Republic of the Congo (DRC) were tested for the presence of IgG antibodies with a peptide-based multiplex mpox serological assay. Results According to stringent or less-stringent cut-off used, 17 to 85 animals (1.1-5.4%) had antibodies to at least one of the three peptides used. Seropositive samples were observed in seven to fifteen species, including Cercopithecus sp (C.ascanius, C.cephus, C.mitis, C.nictitans, C.neglectus, C.pogonias), Cercocebus sp (C.torquatus, C.agilis), Colobus sp (C.angolensis, C.guereza), Papio anubis, Lophocebus albigena, Mandrillus sphinx, Allenopithecus nigroviridis and Pan troglodytes. Mpox seroprevalence was higher in Cameroon than in DRC, i.e. 1.7-8.5% versus 0.2-0.9% (p&lt;0.01 - p&lt;0.001), respectively. Seroprevalence differed also according to sampling sites. In several sites, more than one NHP species was seropositive. Mpox seroprevalence differed, but not significantly in arboreal (1.2-5.4%; 15-69/1,267), semi-terrestrial (1.1-4.3%; 1-4/92) and terrestrial species (0.5-5.7%; 1-12/212). Conclusion The low overall seroprevalence suggests that NHPs are most likely intermediate hosts and may be infected by other species, including reservoirs. However, they remain a potential source of human infection.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"71 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145608731","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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