M Middeldorp,J W Duijster,B J A Hoeve-Bakker,J Berkhof,H E de Melker
BACKGROUNDWe assessed long-term vaccine effectiveness (VE) of 2-dose and 3-dose bivalent HPV vaccination schedules in the Netherlands against incident and persistent HPV infections. Indirect effects of the 3-dose schedule were also assessed.METHODSData from the longitudinal cohort studies HAVANA and HAVANA-2 were used. Women annually provided questionnaires and vaginal samples for HPV determination using the SPF10-DEIA-LiPA25-assay. VEs were assessed using Cox regression over 14 years (3-doses at age 14-16) and 9 years (2-doses at age 12). Changes in 3-dose VE estimates over time were tested. Indirect effects were calculated by comparing unvaccinated participants using Poisson and Cox regression.RESULTSWe included 1,665 HAVANA women and 2,441 HAVANA-2 women. VEs against incident HPV16 and HPV18 infections for 3-doses were 74.3% (95%CI: 56.0-85.0%) and 85.0% (76.1-90.6%) up to 14 years, respectively, and for 2-doses 86.6% (61.6-95.4%) and 95.9% (69.3-99.4%) up to 9 years. For HPV31, VEs were 51.6% (32.7-65.2%) and 58.1% (24.6-76.7%) for 3- and 2-doses, respectively. For HPV45, VEs were 76.1% (54.6-87.4%) and 77.7% (20.2-93.8%). Both schedules showed high VE against persistent HPV16, 18, and 31 infections. Indirect effects among unvaccinated women were 70.1% (49.8-82.2%) for HPV16 and 47.9% (5.0-71.4%) for HPV18.CONCLUSIONWe demonstrated high VE against incident and persistent HPV16 and HPV18 infections up to 14 years after a 3-dose schedule, with no signs of waning and significant indirect effects. Comparable high VEs were found for the 2-dose schedule up to 9 years. Both schedules showed cross-protective effects against persistent HPV31 and HPV45 during prolonged follow-up.
{"title":"The long-term effect of two and three doses of bivalent HPV vaccination against HPV infections: a comparison between two observational cohort studies.","authors":"M Middeldorp,J W Duijster,B J A Hoeve-Bakker,J Berkhof,H E de Melker","doi":"10.1093/infdis/jiag167","DOIUrl":"https://doi.org/10.1093/infdis/jiag167","url":null,"abstract":"BACKGROUNDWe assessed long-term vaccine effectiveness (VE) of 2-dose and 3-dose bivalent HPV vaccination schedules in the Netherlands against incident and persistent HPV infections. Indirect effects of the 3-dose schedule were also assessed.METHODSData from the longitudinal cohort studies HAVANA and HAVANA-2 were used. Women annually provided questionnaires and vaginal samples for HPV determination using the SPF10-DEIA-LiPA25-assay. VEs were assessed using Cox regression over 14 years (3-doses at age 14-16) and 9 years (2-doses at age 12). Changes in 3-dose VE estimates over time were tested. Indirect effects were calculated by comparing unvaccinated participants using Poisson and Cox regression.RESULTSWe included 1,665 HAVANA women and 2,441 HAVANA-2 women. VEs against incident HPV16 and HPV18 infections for 3-doses were 74.3% (95%CI: 56.0-85.0%) and 85.0% (76.1-90.6%) up to 14 years, respectively, and for 2-doses 86.6% (61.6-95.4%) and 95.9% (69.3-99.4%) up to 9 years. For HPV31, VEs were 51.6% (32.7-65.2%) and 58.1% (24.6-76.7%) for 3- and 2-doses, respectively. For HPV45, VEs were 76.1% (54.6-87.4%) and 77.7% (20.2-93.8%). Both schedules showed high VE against persistent HPV16, 18, and 31 infections. Indirect effects among unvaccinated women were 70.1% (49.8-82.2%) for HPV16 and 47.9% (5.0-71.4%) for HPV18.CONCLUSIONWe demonstrated high VE against incident and persistent HPV16 and HPV18 infections up to 14 years after a 3-dose schedule, with no signs of waning and significant indirect effects. Comparable high VEs were found for the 2-dose schedule up to 9 years. Both schedules showed cross-protective effects against persistent HPV31 and HPV45 during prolonged follow-up.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147478970","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}
Jose Mercado Matos,Vickie A Marshall,Elena M Cornejo Castro,Wendell J Miley,Nazzarena Labo,Romin Roshan,Irene Ekwede,Anaida Widell,Ijeoma Agwu,Margaret Namubiru,Matthew Witterholt,Robert Yarchoan,Kathryn Lurain,Denise Whitby,Ramya Ramaswami
BACKGROUNDKaposi sarcoma-associated herpesvirus (KSHV) causes several diseases among people with HIV (PWH), including Kaposi sarcoma (KS), multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and KSHV inflammatory cytokine syndrome (KICS), known as KSHV-associated diseases (KAD). Genetic diversity in the viral K1 gene defines KSHV subtypes, but clinical significance remains unclear.METHODSWe conducted a retrospective study of 143 PWH with KAD treated between 2004-2024. KSHV-DNA was extracted from various clinical samples and sequenced using next-generation and Sanger methods. Phylogenetic analysis was performed to classify K1 subtypes; associations with KAD presentation and survival were assessed.RESULTSAmong 143 patients, 40% had KS alone, 12% had MCD and KS, 17% had KICS and KS and 31% had PEL+/-MCD+/-KS. Subtype A was the most prevalent (46%), followed by C (27%); subtypes did not vary by KAD presentations. Patients with concurrent KAD had worse survival than those with KS alone, irrespective of KSHV subtype. Twenty-one patients with PEL and subtype A had poorer survival outcomes as compared with PEL with other subtypes (median overall survival 1.6 vs. 7.2 years, p=0.0041). Apart from a trend towards lower albumin levels, there were no other differences in clinical characteristics in patients with PEL and Subtype A vs other subtypes.CONCLUSIONSOverall, K1 subtypes did not vary by KAD diagnosis and did not impact survival. Individuals with PEL had poorer outcomes, and subtype A in PEL was associated with worse survival. Further studies are required to investigate the functional impact of KSHV genetic variation on disease pathogenesis.
{"title":"Kaposi sarcoma herpesvirus (KSHV) subtypes and impact on outcomes in KSHV-associated diseases.","authors":"Jose Mercado Matos,Vickie A Marshall,Elena M Cornejo Castro,Wendell J Miley,Nazzarena Labo,Romin Roshan,Irene Ekwede,Anaida Widell,Ijeoma Agwu,Margaret Namubiru,Matthew Witterholt,Robert Yarchoan,Kathryn Lurain,Denise Whitby,Ramya Ramaswami","doi":"10.1093/infdis/jiag168","DOIUrl":"https://doi.org/10.1093/infdis/jiag168","url":null,"abstract":"BACKGROUNDKaposi sarcoma-associated herpesvirus (KSHV) causes several diseases among people with HIV (PWH), including Kaposi sarcoma (KS), multicentric Castleman disease (MCD), primary effusion lymphoma (PEL), and KSHV inflammatory cytokine syndrome (KICS), known as KSHV-associated diseases (KAD). Genetic diversity in the viral K1 gene defines KSHV subtypes, but clinical significance remains unclear.METHODSWe conducted a retrospective study of 143 PWH with KAD treated between 2004-2024. KSHV-DNA was extracted from various clinical samples and sequenced using next-generation and Sanger methods. Phylogenetic analysis was performed to classify K1 subtypes; associations with KAD presentation and survival were assessed.RESULTSAmong 143 patients, 40% had KS alone, 12% had MCD and KS, 17% had KICS and KS and 31% had PEL+/-MCD+/-KS. Subtype A was the most prevalent (46%), followed by C (27%); subtypes did not vary by KAD presentations. Patients with concurrent KAD had worse survival than those with KS alone, irrespective of KSHV subtype. Twenty-one patients with PEL and subtype A had poorer survival outcomes as compared with PEL with other subtypes (median overall survival 1.6 vs. 7.2 years, p=0.0041). Apart from a trend towards lower albumin levels, there were no other differences in clinical characteristics in patients with PEL and Subtype A vs other subtypes.CONCLUSIONSOverall, K1 subtypes did not vary by KAD diagnosis and did not impact survival. Individuals with PEL had poorer outcomes, and subtype A in PEL was associated with worse survival. Further studies are required to investigate the functional impact of KSHV genetic variation on disease pathogenesis.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"4 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471691","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}
Belén Saavedra-Cervera,Dinis Nguenha,Violet Chihota,Getnet Yimer,Carlos Fernández-Escobar,Kathy Mngadi,William Brumskine,Neil Martinson,Shu-Hua Wang,LeeAnne Masilela,Zainab Waggie,Leonardo Martínez,Susan van den Hof,Salome Charalambous,Frank Cobelens,Richard Chaisson,Alison D Grant,Katherine Fielding,Gavin Churchyard,Alberto L Garcia-Basteiro
AIMWe report the longitudinal analysis of QuantiFERON-Gold Plus (QFT-plus) results from a clinical trial conducted in three high TB/HIV burden countries, comparing three different tuberculosis preventive treatment (TPT) regimens in people living with HIV (PLHIV).METHODSPLHIV were enrolled in Ethiopia, Mozambique and South Africa, and randomised to: (i) one course of weekly rifapentine-isoniazid for 3 months (3HP); (ii) weekly rifapentine-isoniazid for 3 months given annually for 2 years (p3HP); (iii) daily isoniazid for 6 months (6H). QFT-plus testing was performed at baseline, M12 and M24. Quantitative and qualitative results, and serial changes (conversions and reversions) were assessed.RESULTSFrom baseline to M12, 13.0% (196/1502) of participants converted, with no differences between 3HP (13.1%) and 6H (12.9%). From M12 to M24 conversion occurred in 4.0% of participants receiving p3HP and 9.4% of those receiving 3HP (p-value 0.110). Overall reversions occurred in 19.0% (178/935) of participants. Reversion rates were similar across study arms and timepoints. The risk of developing TB during the study period was higher among individuals QFT-plus positive at baseline (aHR, 1.66; 95% CI, 1.41-1.89, p-value = 0.034).CONCLUSIONQFT-Plus conversions and reversions occurred frequently in PLHIV and did not differ by TPT regimen, or between those who did and did not receive a second course of TPT. The high rate of QFT-positivity, along with the large proportion of conversions despite TPT highlights the complexity of interpreting serial IGRA results in PLHIV in high-transmission scenarios.
{"title":"Dynamics of Quantiferon-Gold Plus results in a large TB preventive treatment trial across three high-burden HIV/TB countries.","authors":"Belén Saavedra-Cervera,Dinis Nguenha,Violet Chihota,Getnet Yimer,Carlos Fernández-Escobar,Kathy Mngadi,William Brumskine,Neil Martinson,Shu-Hua Wang,LeeAnne Masilela,Zainab Waggie,Leonardo Martínez,Susan van den Hof,Salome Charalambous,Frank Cobelens,Richard Chaisson,Alison D Grant,Katherine Fielding,Gavin Churchyard,Alberto L Garcia-Basteiro","doi":"10.1093/infdis/jiag165","DOIUrl":"https://doi.org/10.1093/infdis/jiag165","url":null,"abstract":"AIMWe report the longitudinal analysis of QuantiFERON-Gold Plus (QFT-plus) results from a clinical trial conducted in three high TB/HIV burden countries, comparing three different tuberculosis preventive treatment (TPT) regimens in people living with HIV (PLHIV).METHODSPLHIV were enrolled in Ethiopia, Mozambique and South Africa, and randomised to: (i) one course of weekly rifapentine-isoniazid for 3 months (3HP); (ii) weekly rifapentine-isoniazid for 3 months given annually for 2 years (p3HP); (iii) daily isoniazid for 6 months (6H). QFT-plus testing was performed at baseline, M12 and M24. Quantitative and qualitative results, and serial changes (conversions and reversions) were assessed.RESULTSFrom baseline to M12, 13.0% (196/1502) of participants converted, with no differences between 3HP (13.1%) and 6H (12.9%). From M12 to M24 conversion occurred in 4.0% of participants receiving p3HP and 9.4% of those receiving 3HP (p-value 0.110). Overall reversions occurred in 19.0% (178/935) of participants. Reversion rates were similar across study arms and timepoints. The risk of developing TB during the study period was higher among individuals QFT-plus positive at baseline (aHR, 1.66; 95% CI, 1.41-1.89, p-value = 0.034).CONCLUSIONQFT-Plus conversions and reversions occurred frequently in PLHIV and did not differ by TPT regimen, or between those who did and did not receive a second course of TPT. The high rate of QFT-positivity, along with the large proportion of conversions despite TPT highlights the complexity of interpreting serial IGRA results in PLHIV in high-transmission scenarios.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"50 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471803","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}
Maulina Hafidzah,Tamiru Shibiru Degaga,Michael Christian,Mohammad Shafiul Alam,Mohammad Sharif Hossain,J Kevin Baird,Inge Sutano,Lauren Smith,Dionne Argyropoulos,Aisah R Amelia,Rintis Noviyanti,Leanne J Robinson,Ric N Price,Ivo Mueller,Kamala Thriemer,Rhea J Longley
BACKGROUNDPlasmodium vivax presents a significant obstacle to malaria elimination due to its capacity to form dormant liver-stage hypnozoites that can cause relapses. Universal radical cure, which administers hypnozoite-targeting treatment to patients with P. falciparum malaria living in co-endemic areas, has potential to reduce P. vivax relapses. However, its implementation is hindered by the lack of a diagnostic tool for detecting hypnozoite-carriage.METHODSP. vivax serological exposure markers (SEMs) were evaluated as a screening tool in P. falciparum patients for predicting risk of P. vivax microscopy-detected episodes over the following 63 days. Analysis was performed using samples from participants in the PRIMA study from Ethiopia, Indonesia, and Bangladesh (NCT03916003). An existing random forest serological classification algorithm was used and evaluated for sensitivity and specificity, then further optimized by re-training a study-specific model.FINDINGSIgG antibodies were measured in 244 P. falciparum participant samples, of which 22 had a vivax microscopy-detected episode during follow-up. SEMs showed high sensitivity (82%) but low specificity (27%), likely due to sustained antibody responses in moderate-to-high transmission areas or undetected sub-microscopic P. vivax infections during follow-up. A study-specific algorithm increased specificity to 68%, but with a corresponding drop in sensitivity to 68%.INTERPRETATIONAlthough P. vivax SEMs showed limited suitability for guiding radical cure in P. falciparum patients in this study (where the outcome was microscopy-detected vivax episodes), they could play a valuable role in building community trust and acceptance of universal radical cure when supported by strong communication and implementation strategies.
{"title":"Predicting risk of Plasmodium vivax microscopy-detected episodes using serological markers in patients with Plasmodium falciparum malaria: a multi-country diagnostic performance evaluation.","authors":"Maulina Hafidzah,Tamiru Shibiru Degaga,Michael Christian,Mohammad Shafiul Alam,Mohammad Sharif Hossain,J Kevin Baird,Inge Sutano,Lauren Smith,Dionne Argyropoulos,Aisah R Amelia,Rintis Noviyanti,Leanne J Robinson,Ric N Price,Ivo Mueller,Kamala Thriemer,Rhea J Longley","doi":"10.1093/infdis/jiag164","DOIUrl":"https://doi.org/10.1093/infdis/jiag164","url":null,"abstract":"BACKGROUNDPlasmodium vivax presents a significant obstacle to malaria elimination due to its capacity to form dormant liver-stage hypnozoites that can cause relapses. Universal radical cure, which administers hypnozoite-targeting treatment to patients with P. falciparum malaria living in co-endemic areas, has potential to reduce P. vivax relapses. However, its implementation is hindered by the lack of a diagnostic tool for detecting hypnozoite-carriage.METHODSP. vivax serological exposure markers (SEMs) were evaluated as a screening tool in P. falciparum patients for predicting risk of P. vivax microscopy-detected episodes over the following 63 days. Analysis was performed using samples from participants in the PRIMA study from Ethiopia, Indonesia, and Bangladesh (NCT03916003). An existing random forest serological classification algorithm was used and evaluated for sensitivity and specificity, then further optimized by re-training a study-specific model.FINDINGSIgG antibodies were measured in 244 P. falciparum participant samples, of which 22 had a vivax microscopy-detected episode during follow-up. SEMs showed high sensitivity (82%) but low specificity (27%), likely due to sustained antibody responses in moderate-to-high transmission areas or undetected sub-microscopic P. vivax infections during follow-up. A study-specific algorithm increased specificity to 68%, but with a corresponding drop in sensitivity to 68%.INTERPRETATIONAlthough P. vivax SEMs showed limited suitability for guiding radical cure in P. falciparum patients in this study (where the outcome was microscopy-detected vivax episodes), they could play a valuable role in building community trust and acceptance of universal radical cure when supported by strong communication and implementation strategies.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"44 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471695","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}
Julia Michalow,Anne Cori,Joshua Kimani,Parinita Bhattacharjee,Marie-Claude Boily,Jeffrey W Imai-Eaton
BACKGROUNDGonorrhoea treatment in sub-Saharan Africa relies on syndromic management, which has poor diagnostic performance and misses asymptomatic infections. Point-of-care tests (POCTs) could address these limitations, but anticipated supply constraints necessitate strategic allocation to maximise impact.METHODSWe developed a deterministic compartmental model of gonorrhoea transmission in Kenya to evaluate allocating POCTs for diagnostic confirmation of symptomatic care attendees versus screening of routine healthcare service attendees across five priority populations: female sex workers (FSW), their male clients (CFSW), pregnant women, adolescent girls and young women, or total population men. We modelled constrained and unrestricted POCT availability during 2025-2030, and estimated infections averted relative to baseline syndromic management. Quality-adjusted life years (QALYs) gained were quantified using probability tree models.RESULTSAt baseline, incidence was highest among FSW (11.9 [UI:5.7-18.6] per 100 per year) and CFSW (13.1 [6.9-24.8]), while most QALY losses (80.6% [76.1-83.8%]) were among pregnant women and their infants. With constrained POCTs (sufficient to test 0.1% of adults annually), diagnostic confirmation averted the most transmission when among symptomatic FSW (2.1% [0.6-5.6%] of infections) or CFSW (2.2% [0.8-5.3%]), and the most morbidity when among symptomatic pregnant women (3.5% [1.8-7.2%] of QALY losses). Screening averted <1% of infections or QALY losses across populations. With unrestricted POCTs, screening had larger absolute impacts but lower per-test efficiency than diagnostic confirmation.CONCLUSIONSOur modelling supports prioritising diagnostic confirmation over screening, consistent with WHO guidance to strengthen aetiologic diagnosis within syndromic care. Diagnostic testing among symptomatic pregnant women had the largest impact on mitigating gonorrhoea-related morbidity.
{"title":"Optimal deployment of gonorrhoea point-of-care tests: modelling the potential impact of diagnostic confirmation testing and screening strategies across five priority populations in Kenya.","authors":"Julia Michalow,Anne Cori,Joshua Kimani,Parinita Bhattacharjee,Marie-Claude Boily,Jeffrey W Imai-Eaton","doi":"10.1093/infdis/jiag162","DOIUrl":"https://doi.org/10.1093/infdis/jiag162","url":null,"abstract":"BACKGROUNDGonorrhoea treatment in sub-Saharan Africa relies on syndromic management, which has poor diagnostic performance and misses asymptomatic infections. Point-of-care tests (POCTs) could address these limitations, but anticipated supply constraints necessitate strategic allocation to maximise impact.METHODSWe developed a deterministic compartmental model of gonorrhoea transmission in Kenya to evaluate allocating POCTs for diagnostic confirmation of symptomatic care attendees versus screening of routine healthcare service attendees across five priority populations: female sex workers (FSW), their male clients (CFSW), pregnant women, adolescent girls and young women, or total population men. We modelled constrained and unrestricted POCT availability during 2025-2030, and estimated infections averted relative to baseline syndromic management. Quality-adjusted life years (QALYs) gained were quantified using probability tree models.RESULTSAt baseline, incidence was highest among FSW (11.9 [UI:5.7-18.6] per 100 per year) and CFSW (13.1 [6.9-24.8]), while most QALY losses (80.6% [76.1-83.8%]) were among pregnant women and their infants. With constrained POCTs (sufficient to test 0.1% of adults annually), diagnostic confirmation averted the most transmission when among symptomatic FSW (2.1% [0.6-5.6%] of infections) or CFSW (2.2% [0.8-5.3%]), and the most morbidity when among symptomatic pregnant women (3.5% [1.8-7.2%] of QALY losses). Screening averted <1% of infections or QALY losses across populations. With unrestricted POCTs, screening had larger absolute impacts but lower per-test efficiency than diagnostic confirmation.CONCLUSIONSOur modelling supports prioritising diagnostic confirmation over screening, consistent with WHO guidance to strengthen aetiologic diagnosis within syndromic care. Diagnostic testing among symptomatic pregnant women had the largest impact on mitigating gonorrhoea-related morbidity.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147471696","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}
BACKGROUNDThe mpox outbreak caused by clade Ib monkeypox virus (MPXV) spread rapidly in Central and East Africa and led the World Health Organization to declare the outbreak a Public Health Emergency of International Concern (PHEIC). In response, China implemented enhanced surveillance measures; nevertheless, an ostensibly asymptomatic returning traveler with repeatedly negative screening tests initiated China's first documented clade Ib mpox transmission cluster.METHODSWe conducted a comprehensive epidemiological, clinical, environmental, and genomic investigation to characterize the transmission pattern and inform public health response strategies. Quantitative PCR, serological testing and whole-genome sequencing were performed on human and environmental samples to confirm infection and assess viral contamination.RESULTSFour epidemiologically linked individuals were identified, including one imported index case, two first-generation confirmed cases resulting from unprotected heterosexual contact with the index case, and one suspected second-generation case associated with intimate contact (overnight co-sleeping). No fever was documented during clinical assessment or follow-up; two cases presented with rash, and one had inguinal lymphadenopathy. Whole-genome sequencing confirmed infection with clade Ib MPXV. All 158 throat swabs collected from general (non-sexual) contacts tested negative. Among 314 environmental samples, 25 of 62 samples collected from case residences were MPXV qPCR-positive, whereas all 252 samples from public settings were negative.CONCLUSIONSThese findings demonstrate that clade Ib mpox transmission can occur from an apparently asymptomatic returning traveler despite repeated negative entry screening, underscoring the limitations of symptom-based or entry-point screening alone and the need for enhanced, risk-based surveillance, diagnostic testing, and targeted prevention strategies.
{"title":"Unnoticed Entry, Noticed Transmission: Epidemiological Insights into China's First clade Ib MPXV cluster.","authors":"Xin Ye,Peng He,Baiyun Yu,Conghua Bai,Jingmin Chen,Qin Liu,Mingming Jiang,Minjie Xiang,Weiwen Guo,Mingqiang Huang,Yiyan Feng,Xiaoliang Guo,Zaiyou Dai,Naling Zhu,Yanjun Chen,Cuihua Fan,Hetao Wang,Tiantian Yin,Yinglin Lin,Duoji Fan,Dongmei Chen,Yuqi Chen,Erbao Bao,Liqing He,Jueyu Wu,Kaibin Wang,Zhigang Han,Wenzhe Su,Bosheng Li,Ximing Huang,Wenfeng Cai","doi":"10.1093/infdis/jiag143","DOIUrl":"https://doi.org/10.1093/infdis/jiag143","url":null,"abstract":"BACKGROUNDThe mpox outbreak caused by clade Ib monkeypox virus (MPXV) spread rapidly in Central and East Africa and led the World Health Organization to declare the outbreak a Public Health Emergency of International Concern (PHEIC). In response, China implemented enhanced surveillance measures; nevertheless, an ostensibly asymptomatic returning traveler with repeatedly negative screening tests initiated China's first documented clade Ib mpox transmission cluster.METHODSWe conducted a comprehensive epidemiological, clinical, environmental, and genomic investigation to characterize the transmission pattern and inform public health response strategies. Quantitative PCR, serological testing and whole-genome sequencing were performed on human and environmental samples to confirm infection and assess viral contamination.RESULTSFour epidemiologically linked individuals were identified, including one imported index case, two first-generation confirmed cases resulting from unprotected heterosexual contact with the index case, and one suspected second-generation case associated with intimate contact (overnight co-sleeping). No fever was documented during clinical assessment or follow-up; two cases presented with rash, and one had inguinal lymphadenopathy. Whole-genome sequencing confirmed infection with clade Ib MPXV. All 158 throat swabs collected from general (non-sexual) contacts tested negative. Among 314 environmental samples, 25 of 62 samples collected from case residences were MPXV qPCR-positive, whereas all 252 samples from public settings were negative.CONCLUSIONSThese findings demonstrate that clade Ib mpox transmission can occur from an apparently asymptomatic returning traveler despite repeated negative entry screening, underscoring the limitations of symptom-based or entry-point screening alone and the need for enhanced, risk-based surveillance, diagnostic testing, and targeted prevention strategies.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461717","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}
Sydney Merritt,Patrick K Mukadi,Jean Paul Kompany,Megan Halbrook,Kamy Musene,Skylar A Martin,Michael Beya,Merly Tambu,Teri Ann S Wong,Jean Jacques Muyembe-Tamfum,Didine K Kaba,Axel T Lehrer,Jason Kindrachuk,Nicole A Hoff,Placide Mbala Kingebeni,Anne W Rimoin
BACKGROUNDOrthomarburgvirus marburgense (MARV) causes infrequent but often fatal disease in humans, with recent outbreaks expanding into new regions including Tanzania, Rwanda and Ethiopia. To date, 18 Marburg virus disease (MVD) outbreaks have been reported, primarily in Sub-Saharan Africa. From 1998-2000, a large MVD outbreak in Watsa/Durba region, Democratic Republic of the Congo (DRC), resulted in 154 confirmed cases and 128 deaths (83% case fatality rate). Given the ongoing public health risks posed by MARV, the lack of approved vaccines and therapeutics, and unpredictable frequency of future outbreaks, this study aimed to assess the prevalence of anti-MARV antibodies in Watsa/Durba.METHODSSamples collected in May 2023, (n=313) included known MVD survivors (n=5), close contacts (n=22) and other residents (n=286). A multiplex immunoassay, was used to assess seroreactivity to MARV antigens and other pan-filovirus targets.RESULTSAmong the Watsa/Durba cohort, 4.5% and 1.6% were seroreactive to MARV glycoprotein (GP) and VP40, respectively, including only one known MVD survivor. No significant associations were found between MARV seroreactivity and risk factors such as travel to Uganda, receiving injections or employment as a gold miner. Of those 14 MARV GP-reactive individuals, 85.7% were cross-reactive to other filoviral targets.CONCLUSIONSThis detected seroprevalence among individuals with no known history of exposure may indicate continued exposure to MARV or MARV-like antigens almost 25 years after the conclusion of the outbreak. Beyond MARV reactivity, detected cross-reactivity to pan-filovirus targets further emphasize a need for increased surveillance, and the potential for asymptomatic, undetected cases in the region.
{"title":"Detection of Marburg Virus Antibodies 25 Years After Outbreak in Watsa, Democratic Republic of the Congo.","authors":"Sydney Merritt,Patrick K Mukadi,Jean Paul Kompany,Megan Halbrook,Kamy Musene,Skylar A Martin,Michael Beya,Merly Tambu,Teri Ann S Wong,Jean Jacques Muyembe-Tamfum,Didine K Kaba,Axel T Lehrer,Jason Kindrachuk,Nicole A Hoff,Placide Mbala Kingebeni,Anne W Rimoin","doi":"10.1093/infdis/jiag155","DOIUrl":"https://doi.org/10.1093/infdis/jiag155","url":null,"abstract":"BACKGROUNDOrthomarburgvirus marburgense (MARV) causes infrequent but often fatal disease in humans, with recent outbreaks expanding into new regions including Tanzania, Rwanda and Ethiopia. To date, 18 Marburg virus disease (MVD) outbreaks have been reported, primarily in Sub-Saharan Africa. From 1998-2000, a large MVD outbreak in Watsa/Durba region, Democratic Republic of the Congo (DRC), resulted in 154 confirmed cases and 128 deaths (83% case fatality rate). Given the ongoing public health risks posed by MARV, the lack of approved vaccines and therapeutics, and unpredictable frequency of future outbreaks, this study aimed to assess the prevalence of anti-MARV antibodies in Watsa/Durba.METHODSSamples collected in May 2023, (n=313) included known MVD survivors (n=5), close contacts (n=22) and other residents (n=286). A multiplex immunoassay, was used to assess seroreactivity to MARV antigens and other pan-filovirus targets.RESULTSAmong the Watsa/Durba cohort, 4.5% and 1.6% were seroreactive to MARV glycoprotein (GP) and VP40, respectively, including only one known MVD survivor. No significant associations were found between MARV seroreactivity and risk factors such as travel to Uganda, receiving injections or employment as a gold miner. Of those 14 MARV GP-reactive individuals, 85.7% were cross-reactive to other filoviral targets.CONCLUSIONSThis detected seroprevalence among individuals with no known history of exposure may indicate continued exposure to MARV or MARV-like antigens almost 25 years after the conclusion of the outbreak. Beyond MARV reactivity, detected cross-reactivity to pan-filovirus targets further emphasize a need for increased surveillance, and the potential for asymptomatic, undetected cases in the region.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"65 2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147461760","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}
Kevin A Brown,Bryan Coburn,Alejandro Hernandez,Bradley J Langford,Valerie Leung,Derek MacFadden,Ashley M Rooney,Kevin L Schwartz,Nick Daneman
BACKGROUNDClostridioides difficile infection (CDI) is principally precipitated by antibiotics, due to their disruption of gut commensal bacteria. The comparative role of nonantibiotic drugs is poorly characterized.METHODSWe examined the contribution of antibiotic and nonantibiotic drugs to CDI risk among residents age >65 years old and not hospitalized in the prior 30 days, between 2018 and 2023. The study used a case-cohort study design, with logistic regression analysis. The case definition consisted of first incident CDI, identified using comprehensive C. difficile testing, hospitalization, and treatment data. Outpatient oral drug exposures were measured in a 1-90-day window prior to case and control days. Adjusted regression models included covariates for age, sex, year and quarter, region, comorbid conditions, healthcare exposures, and drug exposures.RESULTSAmong 16 196 CDI case patients and 549 831 controls, 335 drugs were included. After adjustment, the antibiotics amoxicillin-clavulanate (odds ratio [OR], 6.05 [95% confidence interval (CI), 5.69-6.43]), clindamycin (16.83 [15.53-18.24]), ciprofloxacin (3.83 [3.59-4.09]), and cephalexin (3.05 [2.86-3.25]), were the largest contributors to CDI risk. Nonantibiotic drugs pantoprazole (OR, 1.33 [95% CI, 1.27-1.39]) and ferrous fumarate (1.71 [1.61-1.82]) were the next largest. Metformin had a protective association (OR, 0.67 [95% CI, .63-.72]). In a meta-regression on a subset of 182 drugs, in vitro anticommensal activity was positively associated with CDI risk (P < .001).CONCLUSIONSThis study provides insights into CDI etiology and avenues for stewardship and drug repurposing to combat CDI and antimicrobial resistance.
{"title":"Antibiotic and Nonantibiotic Drugs Associated With Clostridioides difficile Infection Risk: a Pharmacopoeia-Wide Case-Cohort Study.","authors":"Kevin A Brown,Bryan Coburn,Alejandro Hernandez,Bradley J Langford,Valerie Leung,Derek MacFadden,Ashley M Rooney,Kevin L Schwartz,Nick Daneman","doi":"10.1093/infdis/jiag001","DOIUrl":"https://doi.org/10.1093/infdis/jiag001","url":null,"abstract":"BACKGROUNDClostridioides difficile infection (CDI) is principally precipitated by antibiotics, due to their disruption of gut commensal bacteria. The comparative role of nonantibiotic drugs is poorly characterized.METHODSWe examined the contribution of antibiotic and nonantibiotic drugs to CDI risk among residents age >65 years old and not hospitalized in the prior 30 days, between 2018 and 2023. The study used a case-cohort study design, with logistic regression analysis. The case definition consisted of first incident CDI, identified using comprehensive C. difficile testing, hospitalization, and treatment data. Outpatient oral drug exposures were measured in a 1-90-day window prior to case and control days. Adjusted regression models included covariates for age, sex, year and quarter, region, comorbid conditions, healthcare exposures, and drug exposures.RESULTSAmong 16 196 CDI case patients and 549 831 controls, 335 drugs were included. After adjustment, the antibiotics amoxicillin-clavulanate (odds ratio [OR], 6.05 [95% confidence interval (CI), 5.69-6.43]), clindamycin (16.83 [15.53-18.24]), ciprofloxacin (3.83 [3.59-4.09]), and cephalexin (3.05 [2.86-3.25]), were the largest contributors to CDI risk. Nonantibiotic drugs pantoprazole (OR, 1.33 [95% CI, 1.27-1.39]) and ferrous fumarate (1.71 [1.61-1.82]) were the next largest. Metformin had a protective association (OR, 0.67 [95% CI, .63-.72]). In a meta-regression on a subset of 182 drugs, in vitro anticommensal activity was positively associated with CDI risk (P < .001).CONCLUSIONSThis study provides insights into CDI etiology and avenues for stewardship and drug repurposing to combat CDI and antimicrobial resistance.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447062","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}
{"title":"Uncovering the Hidden Impacts of Modern Medicine's Expanding Pharmacopeia on Clostridioides difficile Infection Risk.","authors":"Alison Laufer Halpin,L Clifford McDonald","doi":"10.1093/infdis/jiag011","DOIUrl":"https://doi.org/10.1093/infdis/jiag011","url":null,"abstract":"","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"95 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147447061","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}
Jun Zhou,Xiaoqiong Tang,Liqing He,Fandi Zhang,Xingyu Mou,Ninglin Zhao,Hong Li,Rui Bao
Helicobacter pylori is a significant pathogen associated with a range of diseases, most notably gastritis and gastric cancer, making it a critical target for medical intervention. β-lactam antibiotics, known for their potent bactericidal properties, play a central role in clinical regimens aimed at eradicating H pylori. However, the increasing resistance of H pylori to β-lactams, compounded by the rise of multidrug-resistant strains, presents a major challenge to effective treatment. The molecular mechanisms underlying β-lactam resistance in H pylori are multifactorial, including (1) mutations in penicillin-binding proteins, (2) production of β-lactamases, (3) alterations in outer membrane permeability, and (4) activation of efflux pumps. These mechanisms not only reduce the efficacy of β-lactam antibiotics but also contribute to the emergence of multidrug-resistant H pylori strains. Understanding these molecular pathways is essential for the development of novel therapeutic strategies to overcome resistance and enhance the effectiveness of treatment for H pylori infections.
{"title":"Molecular Mechanisms of β-Lactam Resistance and Its Contribution to Multidrug Resistance in Helicobacter pylori.","authors":"Jun Zhou,Xiaoqiong Tang,Liqing He,Fandi Zhang,Xingyu Mou,Ninglin Zhao,Hong Li,Rui Bao","doi":"10.1093/infdis/jiaf385","DOIUrl":"https://doi.org/10.1093/infdis/jiaf385","url":null,"abstract":"Helicobacter pylori is a significant pathogen associated with a range of diseases, most notably gastritis and gastric cancer, making it a critical target for medical intervention. β-lactam antibiotics, known for their potent bactericidal properties, play a central role in clinical regimens aimed at eradicating H pylori. However, the increasing resistance of H pylori to β-lactams, compounded by the rise of multidrug-resistant strains, presents a major challenge to effective treatment. The molecular mechanisms underlying β-lactam resistance in H pylori are multifactorial, including (1) mutations in penicillin-binding proteins, (2) production of β-lactamases, (3) alterations in outer membrane permeability, and (4) activation of efflux pumps. These mechanisms not only reduce the efficacy of β-lactam antibiotics but also contribute to the emergence of multidrug-resistant H pylori strains. Understanding these molecular pathways is essential for the development of novel therapeutic strategies to overcome resistance and enhance the effectiveness of treatment for H pylori infections.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"16 1","pages":"S10-S20"},"PeriodicalIF":0.0,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147446849","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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