Sun B Sowers,Huong Q Nguyen,Nina B Masters,Sara Mercader,Heather Colley,David L McClure,Carole J Hickman,Mona Marin,Stephen N Crooke
BACKGROUNDA third dose of measles, mumps, and rubella vaccine (MMR3) may be administered in outbreak and nonoutbreak settings. However, data on long-term immunogenicity to the mumps component of MMR are limited. We examined durability of mumps antibody response among adults up to 11 years after receipt of MMR3.METHODSPersons who received MMR3 at ages 18-28 years had sera collected before (baseline), 1 month, 1, 5, and 9-11 years after vaccination. Mumps antibodies were assessed by plaque reduction neutralization, immunoassay (EIA), and immunoglobulin G (IgG) avidity. Neutralizing antibodies were assessed against the vaccine strain (Genotype A) and a wild-type virus from Genotype G. Participants with neutralizing antibody titers <31 for Genotype A and <8 for Genotype G, and with EIA index values <1.10 were considered potentially susceptible.RESULTSAmong participants with data for all visits after MMR3 (40%, n = 262/655), susceptibility based on Genotype A titers increased from 15.7% (41/262) at baseline to 30.5% (80/262) 9-11 years after vaccination while susceptibility based on Genotype G titers remained relatively stable (30.2%-24.2%). The proportion of participants seronegative for mumps IgG by EIA increased from 0% (0/255) at baseline to 7.5% (19/255) 9-11 years after vaccination. The avidity index increased from 52% to 67% through Year 5 (P < .0001).CONCLUSIONSBy 9-11 years after receipt of MMR3, many participants had mumps antibody levels that predicted susceptibility to infection, comparable to those observed before receipt of MMR3. The antibody titers to Genotype G remained consistently lower than the titers to the vaccine strain.
{"title":"Durability of the Mumps Antibody Response After the Third Dose of MMR Vaccine.","authors":"Sun B Sowers,Huong Q Nguyen,Nina B Masters,Sara Mercader,Heather Colley,David L McClure,Carole J Hickman,Mona Marin,Stephen N Crooke","doi":"10.1093/infdis/jiaf520","DOIUrl":"https://doi.org/10.1093/infdis/jiaf520","url":null,"abstract":"BACKGROUNDA third dose of measles, mumps, and rubella vaccine (MMR3) may be administered in outbreak and nonoutbreak settings. However, data on long-term immunogenicity to the mumps component of MMR are limited. We examined durability of mumps antibody response among adults up to 11 years after receipt of MMR3.METHODSPersons who received MMR3 at ages 18-28 years had sera collected before (baseline), 1 month, 1, 5, and 9-11 years after vaccination. Mumps antibodies were assessed by plaque reduction neutralization, immunoassay (EIA), and immunoglobulin G (IgG) avidity. Neutralizing antibodies were assessed against the vaccine strain (Genotype A) and a wild-type virus from Genotype G. Participants with neutralizing antibody titers <31 for Genotype A and <8 for Genotype G, and with EIA index values <1.10 were considered potentially susceptible.RESULTSAmong participants with data for all visits after MMR3 (40%, n = 262/655), susceptibility based on Genotype A titers increased from 15.7% (41/262) at baseline to 30.5% (80/262) 9-11 years after vaccination while susceptibility based on Genotype G titers remained relatively stable (30.2%-24.2%). The proportion of participants seronegative for mumps IgG by EIA increased from 0% (0/255) at baseline to 7.5% (19/255) 9-11 years after vaccination. The avidity index increased from 52% to 67% through Year 5 (P < .0001).CONCLUSIONSBy 9-11 years after receipt of MMR3, many participants had mumps antibody levels that predicted susceptibility to infection, comparable to those observed before receipt of MMR3. The antibody titers to Genotype G remained consistently lower than the titers to the vaccine strain.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"372 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145696839","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}
Pavithra Daulagala, Yonna W Y Leung, Leo L H Luk, Faith Ho, Sofia H N Chu, Jing Lin, Samuel M S Cheng, Nancy H L Leung, Maryna C Eichelberger, Malik Peiris, A Danielle Iuliano, Mark G Thompson, Benjamin J Cowling, Hui-Ling Yen
Background Anti-neuraminidase antibodies have been identified as a correlate of protection for influenza virus infection. We evaluated the immunogenicity of enhanced influenza vaccines versus standard-dose vaccine in inducing neuraminidase inhibition (NAI) antibodies in older adults in a 2-year randomized trial. Methods In 2017/2018, older adults aged 65-82 years in Hong Kong were randomly allocated to receive standard-dose quadrivalent (SD-IIV4), high-dose trivalent (HD-IIV3), MF59-adjuvanted trivalent (aIIV3), or recombinant quadrivalent (RIV4) influenza vaccines of 2017/2018 northern hemisphere formations; HD-IIV3, aIIV3 and RIV4 are enhanced vaccines. NAI antibodies to the 2017/2018 A(H1N1)pdm09 and A(H3N2) vaccine strains were determined from 400 recipients (100 per vaccine group). In 2018/2019, participants were re-randomized to receive the same or a different type of vaccine of northern hemisphere formations. NAI antibodies to the 2018/2019 A(H1N1)pdm09 and A(H3N2) vaccine strains were determined from SD-IIV4 (n=45), HD-IIV3 (n=64), aIIV3 (n=75), or RIV4 (n=29) recipients. NAI antibody titers on the day of vaccination and 30 days post-vaccination were used to compare the geometric mean titer-fold-rise (GMFR) and seroconversion rates of enhanced influenza vaccines versus SD-IIV4. Results SD-IIV4, HD-IIV3, and aIIV3 induced detectable NAI antibodies to both N1 and N2 antigens with GMFR significantly greater than 1. In both years, aIIV3 induced significantly higher GMFR and seroconversion rates to N1 and N2 antigens than SD-IIV4. Notably, individual baseline NAI antibody titers were inversely associated with the post-vaccination antibody titer-fold-rises in all vaccine groups. Conclusions MF-59 adjuvanted aIIV3 induced superior NAI antibody response in older adults than SD-IIV4 in a 2-year randomized trial.
{"title":"Anti-neuraminidase antibody responses in older adults after consecutive vaccinations with enhanced influenza vaccines: a randomized controlled trial","authors":"Pavithra Daulagala, Yonna W Y Leung, Leo L H Luk, Faith Ho, Sofia H N Chu, Jing Lin, Samuel M S Cheng, Nancy H L Leung, Maryna C Eichelberger, Malik Peiris, A Danielle Iuliano, Mark G Thompson, Benjamin J Cowling, Hui-Ling Yen","doi":"10.1093/infdis/jiaf616","DOIUrl":"https://doi.org/10.1093/infdis/jiaf616","url":null,"abstract":"Background Anti-neuraminidase antibodies have been identified as a correlate of protection for influenza virus infection. We evaluated the immunogenicity of enhanced influenza vaccines versus standard-dose vaccine in inducing neuraminidase inhibition (NAI) antibodies in older adults in a 2-year randomized trial. Methods In 2017/2018, older adults aged 65-82 years in Hong Kong were randomly allocated to receive standard-dose quadrivalent (SD-IIV4), high-dose trivalent (HD-IIV3), MF59-adjuvanted trivalent (aIIV3), or recombinant quadrivalent (RIV4) influenza vaccines of 2017/2018 northern hemisphere formations; HD-IIV3, aIIV3 and RIV4 are enhanced vaccines. NAI antibodies to the 2017/2018 A(H1N1)pdm09 and A(H3N2) vaccine strains were determined from 400 recipients (100 per vaccine group). In 2018/2019, participants were re-randomized to receive the same or a different type of vaccine of northern hemisphere formations. NAI antibodies to the 2018/2019 A(H1N1)pdm09 and A(H3N2) vaccine strains were determined from SD-IIV4 (n=45), HD-IIV3 (n=64), aIIV3 (n=75), or RIV4 (n=29) recipients. NAI antibody titers on the day of vaccination and 30 days post-vaccination were used to compare the geometric mean titer-fold-rise (GMFR) and seroconversion rates of enhanced influenza vaccines versus SD-IIV4. Results SD-IIV4, HD-IIV3, and aIIV3 induced detectable NAI antibodies to both N1 and N2 antigens with GMFR significantly greater than 1. In both years, aIIV3 induced significantly higher GMFR and seroconversion rates to N1 and N2 antigens than SD-IIV4. Notably, individual baseline NAI antibody titers were inversely associated with the post-vaccination antibody titer-fold-rises in all vaccine groups. Conclusions MF-59 adjuvanted aIIV3 induced superior NAI antibody response in older adults than SD-IIV4 in a 2-year randomized trial.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145704239","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}
BACKGROUNDWest Nile virus (WNV) infection may result in a serious, neuroinvasive, life-threatening disease. Since there is no known therapy against the virus, treatment is based on supportive care. Little is known about the effect of corticosteroids in West Nile-infected patients, and their use remains controversial.AIMTo evaluate the effect of corticosteroid treatment in West Nile virus-infected patients.METHODSA retrospective cohort study was conducted at Rabin Medical Center, including West Nile virus-infected patients. Data was extracted from patients' electronic medical records. Inverse probability of treatment weighting was used to adjust patient characteristics. Our exposure of interest was corticosteroid prescription during the first 48 hours. IPTW-adjusted Cox proportional hazard models were used to compare the risk of hospital mortality. Secondary outcomes included the need for mechanical ventilation or intensive care unit transfer, and the need for rehabilitation or a long-term care facility at discharge.RESULTSData from 150 confirmed cases were extracted. 41 (27%) patients received corticosteroids. After adjusting for potential confounders, corticosteroid treatment was found to significantly increase hospital mortality (adjusted hazard ratio [aHR] 3.93, 95% confidence interval [CI] 1.14-13.51). A sensitivity analysis including patients with West Nile neuroinvasive disease (WNND) and patients hospitalized for more than 48 hours showed consistent results.CONCLUSIONSOur study suggests that corticosteroid use in WNV patients may be associated with an increased risk of hospital mortality, highlighting the need for caution in their use and further prospective investigation.
{"title":"The Impact of Corticosteroid Therapy on West Nile Virus-Infected Patients: A Retrospective Cohort Study.","authors":"Itamar Poran,Bar Basharim,Yaara Leibovici-Weisman,Michal Michaelis,Nassem Ghantous,Noa Eliakim-Raz","doi":"10.1093/infdis/jiaf601","DOIUrl":"https://doi.org/10.1093/infdis/jiaf601","url":null,"abstract":"BACKGROUNDWest Nile virus (WNV) infection may result in a serious, neuroinvasive, life-threatening disease. Since there is no known therapy against the virus, treatment is based on supportive care. Little is known about the effect of corticosteroids in West Nile-infected patients, and their use remains controversial.AIMTo evaluate the effect of corticosteroid treatment in West Nile virus-infected patients.METHODSA retrospective cohort study was conducted at Rabin Medical Center, including West Nile virus-infected patients. Data was extracted from patients' electronic medical records. Inverse probability of treatment weighting was used to adjust patient characteristics. Our exposure of interest was corticosteroid prescription during the first 48 hours. IPTW-adjusted Cox proportional hazard models were used to compare the risk of hospital mortality. Secondary outcomes included the need for mechanical ventilation or intensive care unit transfer, and the need for rehabilitation or a long-term care facility at discharge.RESULTSData from 150 confirmed cases were extracted. 41 (27%) patients received corticosteroids. After adjusting for potential confounders, corticosteroid treatment was found to significantly increase hospital mortality (adjusted hazard ratio [aHR] 3.93, 95% confidence interval [CI] 1.14-13.51). A sensitivity analysis including patients with West Nile neuroinvasive disease (WNND) and patients hospitalized for more than 48 hours showed consistent results.CONCLUSIONSOur study suggests that corticosteroid use in WNV patients may be associated with an increased risk of hospital mortality, highlighting the need for caution in their use and further prospective investigation.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145674426","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}
After being told that my work was “not independent enough” and that I was “not doing real science,” I began to question how academic medicine defines success. Through teamwork in translational HIV research and community-engaged programs like The Last Gift, I’ve come to see that independence is an illusion, and that collaboration, empathy, and connection are the true engines of discovery and impactful research. This reflection challenges the traditional, hegemonic, metrics of scientific achievement and calls for a broader definition that values mentorship, equity, and collective progress as essential to meaningful science.
{"title":"The Day I Was Told I Wasn’t Doing Science—And Why I’m Grateful for It","authors":"Sara Gianella","doi":"10.1093/infdis/jiaf614","DOIUrl":"https://doi.org/10.1093/infdis/jiaf614","url":null,"abstract":"After being told that my work was “not independent enough” and that I was “not doing real science,” I began to question how academic medicine defines success. Through teamwork in translational HIV research and community-engaged programs like The Last Gift, I’ve come to see that independence is an illusion, and that collaboration, empathy, and connection are the true engines of discovery and impactful research. This reflection challenges the traditional, hegemonic, metrics of scientific achievement and calls for a broader definition that values mentorship, equity, and collective progress as essential to meaningful science.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145680166","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}
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}
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