Pub Date : 2024-10-01DOI: 10.1016/S2666-5247(24)00130-7
Liriye Kurtovic PhD , Gaoqian Feng PhD , Alessia Hysa MBSc , Ali Haghiri PhD , Katherine O’Flaherty PhD , Bruce D Wines PhD , Rebeca Santano PhD , Laura D’Andrea PhD , Prof Heidi E Drummer PhD , Prof P Mark Hogarth PhD , Prof Jahit Sacarlal PhD , Prof Freya J I Fowkes DPhil , Prof Julie A Simpson PhD , Prof Carlota Dobaño PhD , Prof James G Beeson PhD
Background
The RTS,S malaria vaccine is currently recommended for children aged 5–6 months in regions with moderate-to-high Plasmodium falciparum transmission. However, vaccination only confers 55% efficacy over 12 months and wanes within 18 months. The immunological mechanisms of RTS,S-mediated immunity are poorly understood; therefore, we aimed to identify antibody response types associated with protection against malaria in children vaccinated with RTS,S.
Methods
In this post-hoc analysis, we evaluated antibody responses in 737 children aged 1–4 years vaccinated with RTS,S in a phase 2b clinical trial conducted in Mozambique in 2003. We evaluated all available samples collected from children 30 days after the three-dose vaccination schedule at study month 3 (M3; n=737 available of 803 children allocated to receive RTS,S). For comparison, we tested a subset of samples collected before vaccination at study month 0 (M0; n=50) and from children in the control vaccine group (M0 n=25; M3 n=99). We quantified the induction of antibodies to different regions of the vaccine antigen that function by fixing serum complement proteins and binding to Fcγ receptors (FcγRs; FcγRI, FcγRIIa, and FcγRIII) expressed on immune cells as potential mechanisms of immunity.
Findings
Functional antibody responses to the C-terminal region of the vaccine antigen, circumsporozoite protein (CSP), were associated with a reduced risk of malaria (C1q p=0·0060, FcγRIIa p=0·014, and FcγRIII p=0·019). These associations remained significant in male participants when the analyses were stratified by sex (C1q p=0·012, FcγRI p=0·023, FcγRIIa p=0·0070, and FcγRIII p=0·0080). IgA to the central repeat (p=0·0010) and C-terminal (p=0·0040) regions of CSP were also associated with protection. We show that IgA can bind FcαRI and mediate opsonic phagocytosis using a serum pool and monoclonal antibodies. Multiparameter analysis using machine-learning methods suggest that IgA, complement fixation, and FcγRI binding were most predictive of protection against malaria (hazard ratio <1) and suggested that associations differed between male and female participants.
Interpretation
We provide evidence that functional antibody responses mediated by IgG and IgA are associated with protection against malaria in young children vaccinated with RTS,S, and suggest potential differences in the correlates of immunity between males and females. These findings reveal new avenues that could be used to achieve malaria vaccines with higher efficacy.
Funding
National Health and Medical Research Council, Australia, and Thrasher Research Fund.
{"title":"Antibody mechanisms of protection against malaria in RTS,S-vaccinated children: a post-hoc serological analysis of phase 2 trial","authors":"Liriye Kurtovic PhD , Gaoqian Feng PhD , Alessia Hysa MBSc , Ali Haghiri PhD , Katherine O’Flaherty PhD , Bruce D Wines PhD , Rebeca Santano PhD , Laura D’Andrea PhD , Prof Heidi E Drummer PhD , Prof P Mark Hogarth PhD , Prof Jahit Sacarlal PhD , Prof Freya J I Fowkes DPhil , Prof Julie A Simpson PhD , Prof Carlota Dobaño PhD , Prof James G Beeson PhD","doi":"10.1016/S2666-5247(24)00130-7","DOIUrl":"10.1016/S2666-5247(24)00130-7","url":null,"abstract":"<div><h3>Background</h3><div>The RTS,S malaria vaccine is currently recommended for children aged 5–6 months in regions with moderate-to-high <em>Plasmodium falciparum</em> transmission. However, vaccination only confers 55% efficacy over 12 months and wanes within 18 months. The immunological mechanisms of RTS,S-mediated immunity are poorly understood; therefore, we aimed to identify antibody response types associated with protection against malaria in children vaccinated with RTS,S.</div></div><div><h3>Methods</h3><div>In this post-hoc analysis, we evaluated antibody responses in 737 children aged 1–4 years vaccinated with RTS,S in a phase 2b clinical trial conducted in Mozambique in 2003. We evaluated all available samples collected from children 30 days after the three-dose vaccination schedule at study month 3 (M3; n=737 available of 803 children allocated to receive RTS,S). For comparison, we tested a subset of samples collected before vaccination at study month 0 (M0; n=50) and from children in the control vaccine group (M0 n=25; M3 n=99). We quantified the induction of antibodies to different regions of the vaccine antigen that function by fixing serum complement proteins and binding to Fcγ receptors (FcγRs; FcγRI, FcγRIIa, and FcγRIII) expressed on immune cells as potential mechanisms of immunity.</div></div><div><h3>Findings</h3><div>Functional antibody responses to the C-terminal region of the vaccine antigen, circumsporozoite protein (CSP), were associated with a reduced risk of malaria (C1q p=0·0060, FcγRIIa p=0·014, and FcγRIII p=0·019). These associations remained significant in male participants when the analyses were stratified by sex (C1q p=0·012, FcγRI p=0·023, FcγRIIa p=0·0070, and FcγRIII p=0·0080). IgA to the central repeat (p=0·0010) and C-terminal (p=0·0040) regions of CSP were also associated with protection. We show that IgA can bind FcαRI and mediate opsonic phagocytosis using a serum pool and monoclonal antibodies. Multiparameter analysis using machine-learning methods suggest that IgA, complement fixation, and FcγRI binding were most predictive of protection against malaria (hazard ratio <1) and suggested that associations differed between male and female participants.</div></div><div><h3>Interpretation</h3><div>We provide evidence that functional antibody responses mediated by IgG and IgA are associated with protection against malaria in young children vaccinated with RTS,S, and suggest potential differences in the correlates of immunity between males and females. These findings reveal new avenues that could be used to achieve malaria vaccines with higher efficacy.</div></div><div><h3>Funding</h3><div>National Health and Medical Research Council, Australia, and Thrasher Research Fund.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100898"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/j.lanmic.2024.100982
Natalie Elkheir , David A J Moore
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Pub Date : 2024-10-01DOI: 10.1016/S2666-5247(24)00113-7
Harry A Thorpe PhD , Maiju Pesonen PhD , Marta Corbella MSc , Henri Pesonen DSc , Stefano Gaiarsa PhD , Christine J Boinett PhD , Gerry Tonkin-Hill PhD , Tommi Mäklin PhD , Anna K Pöntinen PhD , Neil MacAlasdair PhD , Rebecca A Gladstone PhD , Sergio Arredondo-Alonso PhD , Teemu Kallonen PhD , Dorota Jamrozy PhD , Stephanie W Lo PhD , Chrispin Chaguza PhD , Grace A Blackwell PhD , Prof Antti Honkela PhD , Anita C Schürch PhD , Prof Rob J L Willems , Prof Jukka Corander PhD
<div><h3>Background</h3><div>Nosocomial infections pose a considerable risk to patients who are susceptible, and this is particularly acute in intensive care units when hospital-associated bacteria are endemic. During the first wave of the COVID-19 pandemic, the surge of patients presented a significant obstacle to the effectiveness of infection control measures. We aimed to assess the risks and extent of nosocomial pathogen transmission under a high patient burden by designing a novel bacterial pan-pathogen deep-sequencing approach that could be integrated with standard clinical surveillance and diagnostics workflows.</div></div><div><h3>Methods</h3><div>We did a prospective cohort study in a region of northern Italy that was severely affected by the first wave of the COVID-19 pandemic. Inpatients on both ordinary and intensive care unit (ICU) wards at the San Matteo hospital, Pavia were sampled on multiple occasions to identify bacterial pathogens from respiratory, nasal, and rectal samples. Diagnostic samples collected between April 7 and May 10, 2020 were cultured on six different selective media designed to enrich for <em>Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus,</em> and <em>Streptococcus pneumoniae</em>, and DNA from each plate with positive growth was deep sequenced en masse. We used mSWEEP and mGEMS to bin sequencing reads by sequence cluster for each species, followed by mapping with snippy to generate high quality alignments. Antimicrobial resistance genes were detected by use of ARIBA and CARD. Estimates of hospital transmission were obtained from pairwise bacterial single nucleotide polymorphism distances, partitioned by within-patient and between-patient samples. Finally, we compared the accuracy of our binned <em>Acinetobacter baumannii</em> genomes with those obtained by single colony whole-genome sequencing of isolates from the same hospital.</div></div><div><h3>Findings</h3><div>We recruited patients from March 1 to May 7, 2020. The pathogen population among the patients was large and diverse, with 2148 species detections overall among the 2418 sequenced samples from the 256 patients. In total, 55 sequence clusters from key pathogen species were detected at least five times. The antimicrobial resistance gene prevalence was correspondingly high, with key carbapenemase and extended spectrum ß-lactamase genes detected in at least 50 (40%) of 125 patients in ICUs. Using high-resolution mapping to infer transmission, we established that hospital transmission was likely to be a significant mode of acquisition for each of the pathogen species. Finally, comparison with single colony <em>Acinetobacter baumannii</em> genomes showed that the resolution offered by deep sequencing was equivalent to single-colony sequencing, with the additional benefit of detection of co-colonisation of highly similar strains.</div></div><div><h
{"title":"Pan-pathogen deep sequencing of nosocomial bacterial pathogens in Italy in spring 2020: a prospective cohort study","authors":"Harry A Thorpe PhD , Maiju Pesonen PhD , Marta Corbella MSc , Henri Pesonen DSc , Stefano Gaiarsa PhD , Christine J Boinett PhD , Gerry Tonkin-Hill PhD , Tommi Mäklin PhD , Anna K Pöntinen PhD , Neil MacAlasdair PhD , Rebecca A Gladstone PhD , Sergio Arredondo-Alonso PhD , Teemu Kallonen PhD , Dorota Jamrozy PhD , Stephanie W Lo PhD , Chrispin Chaguza PhD , Grace A Blackwell PhD , Prof Antti Honkela PhD , Anita C Schürch PhD , Prof Rob J L Willems , Prof Jukka Corander PhD","doi":"10.1016/S2666-5247(24)00113-7","DOIUrl":"10.1016/S2666-5247(24)00113-7","url":null,"abstract":"<div><h3>Background</h3><div>Nosocomial infections pose a considerable risk to patients who are susceptible, and this is particularly acute in intensive care units when hospital-associated bacteria are endemic. During the first wave of the COVID-19 pandemic, the surge of patients presented a significant obstacle to the effectiveness of infection control measures. We aimed to assess the risks and extent of nosocomial pathogen transmission under a high patient burden by designing a novel bacterial pan-pathogen deep-sequencing approach that could be integrated with standard clinical surveillance and diagnostics workflows.</div></div><div><h3>Methods</h3><div>We did a prospective cohort study in a region of northern Italy that was severely affected by the first wave of the COVID-19 pandemic. Inpatients on both ordinary and intensive care unit (ICU) wards at the San Matteo hospital, Pavia were sampled on multiple occasions to identify bacterial pathogens from respiratory, nasal, and rectal samples. Diagnostic samples collected between April 7 and May 10, 2020 were cultured on six different selective media designed to enrich for <em>Acinetobacter baumannii, Escherichia coli, Enterococcus faecium, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus,</em> and <em>Streptococcus pneumoniae</em>, and DNA from each plate with positive growth was deep sequenced en masse. We used mSWEEP and mGEMS to bin sequencing reads by sequence cluster for each species, followed by mapping with snippy to generate high quality alignments. Antimicrobial resistance genes were detected by use of ARIBA and CARD. Estimates of hospital transmission were obtained from pairwise bacterial single nucleotide polymorphism distances, partitioned by within-patient and between-patient samples. Finally, we compared the accuracy of our binned <em>Acinetobacter baumannii</em> genomes with those obtained by single colony whole-genome sequencing of isolates from the same hospital.</div></div><div><h3>Findings</h3><div>We recruited patients from March 1 to May 7, 2020. The pathogen population among the patients was large and diverse, with 2148 species detections overall among the 2418 sequenced samples from the 256 patients. In total, 55 sequence clusters from key pathogen species were detected at least five times. The antimicrobial resistance gene prevalence was correspondingly high, with key carbapenemase and extended spectrum ß-lactamase genes detected in at least 50 (40%) of 125 patients in ICUs. Using high-resolution mapping to infer transmission, we established that hospital transmission was likely to be a significant mode of acquisition for each of the pathogen species. Finally, comparison with single colony <em>Acinetobacter baumannii</em> genomes showed that the resolution offered by deep sequencing was equivalent to single-colony sequencing, with the additional benefit of detection of co-colonisation of highly similar strains.</div></div><div><h","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100890"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S2666-5247(24)00126-5
Xiaoli Pang PhD , Bonita E Lee MD , Tiejun Gao PhD , Rhonda J Rosychuk PhD , Linnet Immaraj PhD , Judy Y Qiu PhD , Jiabi Wen MS , Nathan Zelyas MD , Krista Howden DACVPM , Janelle Wallace MPh , Eleanor Risling MD , Lorie A Little MD , John Kim PhD , Heidi Wood PhD , Alyssia Robinson BA , Michael Parkins MD , Casey R J Hubert PhD , Kevin Frankowski MS , Steve E Hrudey Dsc [Eng] , Christopher Sikora MD
Background
The unprecedented COVID-19 pandemic has highlighted the strategic value of wastewater-based surveillance (WBS) of SARS-CoV-2. This multisite 28-month-long study focused on WBS for older residents in 12 long-term care facilities (LTCFs) in Edmonton (AB, Canada) by assessing relationships between COVID-19, WBS, and serostatus during the pandemic.
Methods
Wastewater samples collected two to three times per week were tested for SARS-CoV-2 using RT-quantitative PCR. The serostatus of antibodies was examined using immunoassays. The data of clinical COVID-19 outbreaks based on extensive testing were obtained from local public health officials. Analyses included calculating correlations between 7-day rolling averages for WBS and COVID-19 cases and investigating whether WBS led or lagged confirmed outbreaks using a multinomial test.
Findings
Wastewater results correlated well with clinical COVID-19 infections and outbreaks at participating LTCFs. 1058 (36·0%) of 2936 collected wastewater samples were SARS-CoV-2 positive, compared with 1247 people (resident n=671, staff n=572, and unknown n=4) reporting positive test results of 21 673 clinical samples assessed (5·8%). WBS led clinical testing in 32 (60·4%) confirmed outbreaks, which was significantly different from WBS lagged (12 outbreaks [22·6%, 95% CI 11·3–33·7]). Non-detection of WBS SARS-CoV-2 served as a negative predictor for outbreaks. WBS results attested protective immunity in vaccinated individuals before the omicron wave. A parallel increase in the proportions of positive WBS SARS-CoV-2 and anti-nucleocapsid antibodies underlined that omicron was an immunity-evading variant despite high seropositivity of neutralising antibodies after multiple doses of vaccine.
Interpretation
Implementation of WBS could enable targeted clinical investigations and improve cost-effectiveness of COVID-19 outbreak management in LTCFs. WBS and serostatus provided informed dynamic changes of infections and immunity. Critical evidence was that LTCF WBS is an effective early warning system to support rapid public health outbreak management and protect vulnerable older populations.
Funding
Canadian Immunity Task Force for COVID-19 and Alberta Health.
{"title":"Early warning COVID-19 outbreak in long-term care facilities using wastewater surveillance: correlation, prediction, and interaction with clinical and serological statuses","authors":"Xiaoli Pang PhD , Bonita E Lee MD , Tiejun Gao PhD , Rhonda J Rosychuk PhD , Linnet Immaraj PhD , Judy Y Qiu PhD , Jiabi Wen MS , Nathan Zelyas MD , Krista Howden DACVPM , Janelle Wallace MPh , Eleanor Risling MD , Lorie A Little MD , John Kim PhD , Heidi Wood PhD , Alyssia Robinson BA , Michael Parkins MD , Casey R J Hubert PhD , Kevin Frankowski MS , Steve E Hrudey Dsc [Eng] , Christopher Sikora MD","doi":"10.1016/S2666-5247(24)00126-5","DOIUrl":"10.1016/S2666-5247(24)00126-5","url":null,"abstract":"<div><h3>Background</h3><div>The unprecedented COVID-19 pandemic has highlighted the strategic value of wastewater-based surveillance (WBS) of SARS-CoV-2. This multisite 28-month-long study focused on WBS for older residents in 12 long-term care facilities (LTCFs) in Edmonton (AB, Canada) by assessing relationships between COVID-19, WBS, and serostatus during the pandemic.</div></div><div><h3>Methods</h3><div>Wastewater samples collected two to three times per week were tested for SARS-CoV-2 using RT-quantitative PCR. The serostatus of antibodies was examined using immunoassays. The data of clinical COVID-19 outbreaks based on extensive testing were obtained from local public health officials. Analyses included calculating correlations between 7-day rolling averages for WBS and COVID-19 cases and investigating whether WBS led or lagged confirmed outbreaks using a multinomial test.</div></div><div><h3>Findings</h3><div>Wastewater results correlated well with clinical COVID-19 infections and outbreaks at participating LTCFs. 1058 (36·0%) of 2936 collected wastewater samples were SARS-CoV-2 positive, compared with 1247 people (resident n=671, staff n=572, and unknown n=4) reporting positive test results of 21 673 clinical samples assessed (5·8%). WBS led clinical testing in 32 (60·4%) confirmed outbreaks, which was significantly different from WBS lagged (12 outbreaks [22·6%, 95% CI 11·3–33·7]). Non-detection of WBS SARS-CoV-2 served as a negative predictor for outbreaks. WBS results attested protective immunity in vaccinated individuals before the omicron wave. A parallel increase in the proportions of positive WBS SARS-CoV-2 and anti-nucleocapsid antibodies underlined that omicron was an immunity-evading variant despite high seropositivity of neutralising antibodies after multiple doses of vaccine.</div></div><div><h3>Interpretation</h3><div>Implementation of WBS could enable targeted clinical investigations and improve cost-effectiveness of COVID-19 outbreak management in LTCFs. WBS and serostatus provided informed dynamic changes of infections and immunity. Critical evidence was that LTCF WBS is an effective early warning system to support rapid public health outbreak management and protect vulnerable older populations.</div></div><div><h3>Funding</h3><div>Canadian Immunity Task Force for COVID-19 and Alberta Health.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100894"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056886","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S2666-5247(24)00136-8
{"title":"Oropouche fever outbreak in Brazil: an emerging concern in Latin America","authors":"","doi":"10.1016/S2666-5247(24)00136-8","DOIUrl":"10.1016/S2666-5247(24)00136-8","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100904"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S2666-5247(24)00160-5
Prof Jonathan J Juliano MD , David J Giesbrecht PhD , Alfred Simkin PhD , Abebe A Fola PhD , Beatus M Lyimo PhD , Dativa Pereus MSc , Catherine Bakari MSc , Rashid A Madebe MSc , Misago D Seth PhD , Celine I Mandara PhD , Zachary R Popkin-Hall PhD , Ramadhan Moshi BSc , Ruth B Mbwambo BSc , Karamoko Niaré PhD , Bronwyn MacInnis PhD , Filbert Francis PhD , Daniel Mbwambo MSc , Issa Garimo MSc , Frank Chacky MSc , Sijenunu Aaron MSc , Prof Deus S Ishengoma PhD
<div><h3>Background</h3><div>The emergence of the artemisinin partial resistance (ART-R) mutation in the <em>Plasmodium falciparum kelch13</em> gene (<em>k13</em>), Arg561His, in Rwanda and the regional presence of polymorphisms affecting sulfadoxine–pyrimethamine have raised concern in neighbouring Tanzania. The goal of this study was to assess the status of antimalarial resistance in Tanzania, with a focus on the border with Rwanda, to understand the distribution of the Arg561His mutation, partner drug resistance, and resistance to chemoprevention drugs.</div></div><div><h3>Methods</h3><div>In this cross-sectional survey, capillary dried blood spots were collected from malaria positive asymptomatic individuals in the community and symptomatic individuals in health facilities aged 6 months and older, in 13 regions of mainland Tanzania from Jan 31 to June 26, 2021. Exclusion criteria included residence of the areas other than the target sites, presenting to the health facility for care and treatment of conditions other than malaria, and not providing informed consent. Samples were assessed for antimalarial resistance polymorphisms and genetic relatedness using molecular inversion probes targeting <em>P falciparum</em> and short-read whole-genome sequencing. The primary outcome was the prevalence of molecular markers of antimalarial resistance at the region level, as well as at the district level in Kagera, a region in the northwest of the country at the border with Rwanda.</div></div><div><h3>Findings</h3><div>6855 (88·1%) of 7782 capillary dried blood spot samples collected were successfully genotyped. The overall prevalence of <em>k13</em> Arg561His in Kagera was 7·7% (90% CI 6·0–9·4; 50 of 649), with the highest prevalence in the districts near the Rwandan border (22·8% [31 of 136] in Karagwe, 14·4% [17 of 118]) in Kyerwa, and 1·4% [two of 144] in Ngara). <em>k13</em> Arg561His was uncommon in the other regions. Haplotype analysis suggested that some of these parasites are related to isolates collected in Rwanda in 2015, supporting regional spread of Arg561His. However, a novel <em>k13</em> Arg561His haplotype was observed, potentially indicating a second origin in the region. Other validated <em>k13</em> resistance polymorphisms (one Arg622Ile and two Ala675Val isolates) were also identified. A region of prevalent dihydrofolate reductase Ile164Leu mutation, associated with sulfadoxine–pyrimethamine resistance, was also identified in Kagera (15·2% [12·6–17·8%]; 80 of 526). The mutant <em>crt</em> Lys76Thr mutation, associated with chloroquine and amodiaquine resistance, was uncommon, occurring only in 75 of 2861 genotyped isolates, whereases the wild-type <em>mdr1</em> Asn86Tyr allele, associated with reduced sensitivity to lumefantrine, was found in 99·7% (3819 of 3830) of samples countrywide.</div></div><div><h3>Interpretation</h3><div>These findings show that the <em>k13</em> Arg561His mutation is common in northwest Tanzania and that multi
{"title":"Prevalence of mutations associated with artemisinin partial resistance and sulfadoxine–pyrimethamine resistance in 13 regions in Tanzania in 2021: a cross-sectional survey","authors":"Prof Jonathan J Juliano MD , David J Giesbrecht PhD , Alfred Simkin PhD , Abebe A Fola PhD , Beatus M Lyimo PhD , Dativa Pereus MSc , Catherine Bakari MSc , Rashid A Madebe MSc , Misago D Seth PhD , Celine I Mandara PhD , Zachary R Popkin-Hall PhD , Ramadhan Moshi BSc , Ruth B Mbwambo BSc , Karamoko Niaré PhD , Bronwyn MacInnis PhD , Filbert Francis PhD , Daniel Mbwambo MSc , Issa Garimo MSc , Frank Chacky MSc , Sijenunu Aaron MSc , Prof Deus S Ishengoma PhD","doi":"10.1016/S2666-5247(24)00160-5","DOIUrl":"10.1016/S2666-5247(24)00160-5","url":null,"abstract":"<div><h3>Background</h3><div>The emergence of the artemisinin partial resistance (ART-R) mutation in the <em>Plasmodium falciparum kelch13</em> gene (<em>k13</em>), Arg561His, in Rwanda and the regional presence of polymorphisms affecting sulfadoxine–pyrimethamine have raised concern in neighbouring Tanzania. The goal of this study was to assess the status of antimalarial resistance in Tanzania, with a focus on the border with Rwanda, to understand the distribution of the Arg561His mutation, partner drug resistance, and resistance to chemoprevention drugs.</div></div><div><h3>Methods</h3><div>In this cross-sectional survey, capillary dried blood spots were collected from malaria positive asymptomatic individuals in the community and symptomatic individuals in health facilities aged 6 months and older, in 13 regions of mainland Tanzania from Jan 31 to June 26, 2021. Exclusion criteria included residence of the areas other than the target sites, presenting to the health facility for care and treatment of conditions other than malaria, and not providing informed consent. Samples were assessed for antimalarial resistance polymorphisms and genetic relatedness using molecular inversion probes targeting <em>P falciparum</em> and short-read whole-genome sequencing. The primary outcome was the prevalence of molecular markers of antimalarial resistance at the region level, as well as at the district level in Kagera, a region in the northwest of the country at the border with Rwanda.</div></div><div><h3>Findings</h3><div>6855 (88·1%) of 7782 capillary dried blood spot samples collected were successfully genotyped. The overall prevalence of <em>k13</em> Arg561His in Kagera was 7·7% (90% CI 6·0–9·4; 50 of 649), with the highest prevalence in the districts near the Rwandan border (22·8% [31 of 136] in Karagwe, 14·4% [17 of 118]) in Kyerwa, and 1·4% [two of 144] in Ngara). <em>k13</em> Arg561His was uncommon in the other regions. Haplotype analysis suggested that some of these parasites are related to isolates collected in Rwanda in 2015, supporting regional spread of Arg561His. However, a novel <em>k13</em> Arg561His haplotype was observed, potentially indicating a second origin in the region. Other validated <em>k13</em> resistance polymorphisms (one Arg622Ile and two Ala675Val isolates) were also identified. A region of prevalent dihydrofolate reductase Ile164Leu mutation, associated with sulfadoxine–pyrimethamine resistance, was also identified in Kagera (15·2% [12·6–17·8%]; 80 of 526). The mutant <em>crt</em> Lys76Thr mutation, associated with chloroquine and amodiaquine resistance, was uncommon, occurring only in 75 of 2861 genotyped isolates, whereases the wild-type <em>mdr1</em> Asn86Tyr allele, associated with reduced sensitivity to lumefantrine, was found in 99·7% (3819 of 3830) of samples countrywide.</div></div><div><h3>Interpretation</h3><div>These findings show that the <em>k13</em> Arg561His mutation is common in northwest Tanzania and that multi","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100920"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142005520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S2666-5247(24)00109-5
In June, 2023, the Council of the EU published a recommendation that the European Commission should contribute to the design and governance of an EU cross-country pull incentive to stimulate antimicrobial innovation and access. In this Personal View, we discuss six key considerations to support the implementation of the new pull incentive—ie, the size of the potential pull incentive and possible contributions of the member states, design of the incentive model, interplay of the new pull incentive with the proposed revisions of the EU pharmaceutical legislation, roles and responsibilities of both the EU and member states, balance between pull and push incentives, and global cooperation and responsibility. As the involvement of the member states with the EU pull incentive will be voluntary, member states should have confidence that the processes used to identify eligible antimicrobials, negotiate terms and conditions, and oversee access agreements are transparent, inclusive, and methodologically robust.
{"title":"Implementing an EU pull incentive for antimicrobial innovation and access: blueprint for action","authors":"","doi":"10.1016/S2666-5247(24)00109-5","DOIUrl":"10.1016/S2666-5247(24)00109-5","url":null,"abstract":"<div><div>In June, 2023, the Council of the EU published a recommendation that the European Commission should contribute to the design and governance of an EU cross-country pull incentive to stimulate antimicrobial innovation and access. In this Personal View, we discuss six key considerations to support the implementation of the new pull incentive—ie, the size of the potential pull incentive and possible contributions of the member states, design of the incentive model, interplay of the new pull incentive with the proposed revisions of the EU pharmaceutical legislation, roles and responsibilities of both the EU and member states, balance between pull and push incentives, and global cooperation and responsibility. As the involvement of the member states with the EU pull incentive will be voluntary, member states should have confidence that the processes used to identify eligible antimicrobials, negotiate terms and conditions, and oversee access agreements are transparent, inclusive, and methodologically robust.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100886"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141399355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1016/S2666-5247(24)00103-4
{"title":"Used antigenic devices as a matrix for molecular detection of respiratory viruses","authors":"","doi":"10.1016/S2666-5247(24)00103-4","DOIUrl":"10.1016/S2666-5247(24)00103-4","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100880"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140909507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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