Pub Date : 2026-02-23DOI: 10.1016/j.lanmic.2025.101307
Maurine Murtagh, P Lewis White, Juan Luis Rodriguez-Tudela, Ana Alastruey-Izquierdo, Sharon C-A Chen, Philippe J Dufresne, Beatriz L Gómez, Guillermo Garcia-Effron, Betsy Wonderly Trainor, Pilar Garcia-Vello, Till T Bachmann, Pascale Ondoa, Daniel Marcano Zamora, Tamarie Rocke, Alexandra Cameron, Valeria Gigante
Invasive fungal diseases (IFDs) are a growing global health threat, particularly in low-income and middle-income countries (LMICs), where diagnostic capacity is limited. The emergence and spread of antifungal resistance further complicate clinical management. Despite the high burden of IFDs, diagnostic development for fungal pathogens has lagged compared with that for its bacterial and viral counterparts. In this Review, we synthesised findings from WHO's 2024 diagnostic landscape analysis of fungal priority pathogens. We discussed the availability, accessibility, and performance of the current diagnostic tools, including phenotypic, immunological, and molecular methods, and identified key gaps in LMICs. WHO's research and development priorities for diagnostics for LMICs are also presented herein. The assessment reveals that most diagnostic platforms for IFDs are culture dependent, infrastructure intensive, and inaccessible at primary and secondary health-care levels in LMICs. Non-culture-based methods, such as lateral flow immunoassays and molecular diagnostics, are promising, but remain restricted in scope, species coverage, and affordability. Multiplex platforms capable of simultaneous broad pathogen detection and antifungal resistance testing are scarce. WHO has identified priority areas for diagnostic innovation, including simplified lateral flow immunoassays, automated culture systems, and integrated molecular platforms suitable for use in LMICs. Addressing diagnostic gaps for IFDs requires targeted investment in simplified, rapid, and affordable diagnostic tools that can be deployed across multiple levels of health-care system. WHO's research and development priorities aim to guide diagnostic developers and public health stakeholders in accelerating innovation and improving access to fungal diagnostics, particularly in LMICs, to reduce IFD-related morbidity and mortality.
{"title":"Global perspective on gaps in fungal diagnostics in low-resource settings: WHO landscape analysis and research priorities for invasive fungal diseases.","authors":"Maurine Murtagh, P Lewis White, Juan Luis Rodriguez-Tudela, Ana Alastruey-Izquierdo, Sharon C-A Chen, Philippe J Dufresne, Beatriz L Gómez, Guillermo Garcia-Effron, Betsy Wonderly Trainor, Pilar Garcia-Vello, Till T Bachmann, Pascale Ondoa, Daniel Marcano Zamora, Tamarie Rocke, Alexandra Cameron, Valeria Gigante","doi":"10.1016/j.lanmic.2025.101307","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101307","url":null,"abstract":"<p><p>Invasive fungal diseases (IFDs) are a growing global health threat, particularly in low-income and middle-income countries (LMICs), where diagnostic capacity is limited. The emergence and spread of antifungal resistance further complicate clinical management. Despite the high burden of IFDs, diagnostic development for fungal pathogens has lagged compared with that for its bacterial and viral counterparts. In this Review, we synthesised findings from WHO's 2024 diagnostic landscape analysis of fungal priority pathogens. We discussed the availability, accessibility, and performance of the current diagnostic tools, including phenotypic, immunological, and molecular methods, and identified key gaps in LMICs. WHO's research and development priorities for diagnostics for LMICs are also presented herein. The assessment reveals that most diagnostic platforms for IFDs are culture dependent, infrastructure intensive, and inaccessible at primary and secondary health-care levels in LMICs. Non-culture-based methods, such as lateral flow immunoassays and molecular diagnostics, are promising, but remain restricted in scope, species coverage, and affordability. Multiplex platforms capable of simultaneous broad pathogen detection and antifungal resistance testing are scarce. WHO has identified priority areas for diagnostic innovation, including simplified lateral flow immunoassays, automated culture systems, and integrated molecular platforms suitable for use in LMICs. Addressing diagnostic gaps for IFDs requires targeted investment in simplified, rapid, and affordable diagnostic tools that can be deployed across multiple levels of health-care system. WHO's research and development priorities aim to guide diagnostic developers and public health stakeholders in accelerating innovation and improving access to fungal diagnostics, particularly in LMICs, to reduce IFD-related morbidity and mortality.</p>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101307"},"PeriodicalIF":20.4,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147311164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-10DOI: 10.1016/j.lanmic.2026.101370
Zhiying Ou, Xianggao Hu, Siying Cao, Xi Xue, Kangpeng Xiao
{"title":"Cryptic diversity of coronaviruses in urban wastewater in central China.","authors":"Zhiying Ou, Xianggao Hu, Siying Cao, Xi Xue, Kangpeng Xiao","doi":"10.1016/j.lanmic.2026.101370","DOIUrl":"https://doi.org/10.1016/j.lanmic.2026.101370","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101370"},"PeriodicalIF":20.4,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146195818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1016/j.lanmic.2026.101348
Talha Burki
{"title":"Spike in diphtheria in Africa raises concerns.","authors":"Talha Burki","doi":"10.1016/j.lanmic.2026.101348","DOIUrl":"https://doi.org/10.1016/j.lanmic.2026.101348","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101348"},"PeriodicalIF":20.4,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-02-05DOI: 10.1016/j.lanmic.2025.101270
Prof Magnus Unemo PhD , Daniel Golparian MSc , Varalakshmi Elango MD , Esther Bettiol MD , Prof Laura J V Piddock PhD , Subasree Srinivasan MD , Patricia A Bradford PhD , Samir H Moussa PhD , Sarah M McLeod PhD , John P Mueller PhD , Prof Edward W Hook III MD , Alison Luckey MD
<div><h3>Background</h3><div>Zoliflodacin, a first-in-class oral bacterial, DNA gyrase (GyrB) inhibitor, showed non-inferiority to ceftriaxone combined with azithromycin in a recent large international, phase 3, randomised controlled trial for treatment of uncomplicated urogenital gonorrhoea. The aim of this study was to describe the microbiological and whole-genome sequencing (WGS) analyses of paired baseline (pre-treatment) and test-of-cure (TOC) gonococcal isolates from the zoliflodacin phase 3, randomised controlled trial to further characterise and evaluate the protocol-specified microbiological failures with zoliflodacin (n=22) or ceftriaxone and azithromycin (n=1).</div></div><div><h3>Methods</h3><div>In this retrospective, genomic, observational study, results from antimicrobial susceptibility testing (agar dilution method) of isolates (n=960; 936 baseline isolates from 763 participants and 24 TOC isolates [23 with a paired baseline isolate in the same anatomical site] from 20 participants) collected during the zoliflodacin phase 3, randomised controlled trial done in 16 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA (Nov 6, 2019–March 16, 2023) are described. WGS analysis was performed on paired baseline and TOC isolates from participants with microbiological failures (zoliflodacin 44 isolates [19 participants]; ceftriaxone and azithromycin two isolates [one participant]), and the three baseline isolates with highest zoliflodacin minimum inhibitory concentration (MIC 0·5 mg/L).</div></div><div><h3>Findings</h3><div>All isolates were inhibited by the same zoliflodacin concentrations (MICs ≤0·008 to 0·5 mg/L) as wild-type strains cultured internationally in 2013–23. In participants with a microbiological failure after zoliflodacin treatment (n=22, 19 participants), zoliflodacin MIC values for baseline and TOC isolates were similar, and resistance selection was lacking. WGS showed that five (23%) of 22 infections (95% CI 10–43 [in four participants]) of zoliflodacin microbiological failures had different strains at TOC versus baseline. In 17 zoliflodacin microbiological failures (15 participants), isolates at baseline and TOC were indistinguishable. 13 of these 17 microbiological failures, corresponding to 59% (95% CI 39–77; 13 of 22) of all zoliflodacin microbiological failures, were in urogenital or rectal sites in 11 participants and the isolates had zoliflodacin MICs less than or equal to 0·008 to 0·25 mg/L. The single microbiological failure after ceftriaxone and azithromycin treatment had different strains at TOC versus at baseline. No sequenced isolates had mutations associated with elevated zoliflodacin MICs.</div></div><div><h3>Interpretation</h3><div>In the zoliflodacin phase 3, randomised controlled trial, 23% of the zoliflodacin microbiological failures and the single ceftriaxone and azithromycin microbiological failure had different gonococcal strains at TOC versus baseline, which suggests r
背景：Zoliflodacin是一种一流的口服细菌DNA回转酶（GyrB）抑制剂，在最近的一项大型国际3期随机对照试验中，Zoliflodacin治疗无并发症泌尿生殖器淋病的效果优于头孢曲松联合阿奇霉素。本研究的目的是描述来自唑氟哌啶3期随机对照试验的配对基线（预处理）和治愈试验（TOC）淋球菌分离物的微生物学和全基因组测序（WGS）分析，以进一步表征和评估方案指定的使用唑氟哌啶（n=22）或头孢曲松和阿奇霉素（n=1）的微生物学失败。方法：在这项回顾性、基因组学、观察性研究中，分离株(n=960；本文描述了唑氟哌啶三期随机对照试验（2019年11月6日- 2023年3月16日）在比利时、荷兰、南非、泰国和美国的16家门诊诊所进行的936株基线分离株和24株TOC分离株（23株基线分离株位于同一解剖部位），分别来自763名参与者和20名参与者。WGS分析了来自微生物学失败的受试者的配对基线和TOC分离株（唑氟哌啶44株[19名受试者]；头孢曲松和阿奇霉素2株[1名受试者]），以及唑氟哌啶最低抑制浓度最高的3株基线分离株（MIC为0.5 mg/L）。结果：2013-23年国际上培养的唑氟菌素浓度（mic≤0.008 ~ 0.05 mg/L）与野生型菌株相同，所有菌株均有抑制作用。在唑氟达星治疗后微生物学失败的参与者中（n= 22,19名参与者），基线和TOC分离株的唑氟达星MIC值相似，缺乏耐药选择。WGS显示，22例唑氟西林微生物学失败的感染中有5例（23%）（95% CI 10-43[4名参与者]）在TOC与基线时的菌株不同。在17例唑氟西林微生物学失败（15例参与者）中，基线和TOC的分离物无法区分。这17例微生物学失败中有13例发生在11例受试者的泌尿生殖器或直肠部位，占所有唑氟达星微生物学失败的59% （95% CI 39-77； 22例中的13例），分离株的唑氟达星mic小于或等于0.008 ~ 0.25 mg/L。头孢曲松和阿奇霉素治疗后的单一微生物失败在TOC与基线时有不同的菌株。没有测序的分离株具有与唑氟达星mic升高相关的突变。解释：在唑氟菌素3期随机对照试验中，23%的唑氟菌素微生物学失败以及头孢曲松和阿奇霉素单一微生物学失败的淋球菌菌株在TOC与基线时不同，这表明再感染而不是治疗失败。此外，59%的唑氟哌啶微生物学失败（均发生在肛门生殖器部位），基于低唑氟哌啶mic、既往药效学研究以及唑氟哌啶治疗后耐药性选择的证据，没有明显的微生物学解释。不能排除再感染是这些微生物失效的原因。我们建议在未来淋病治疗的随机对照试验中实施WGS，以进一步评估可能的微生物学失败，排除再感染（以避免低估治愈率），并确定抗菌素耐药性决定因素。资助：GARDP通过德国BMFTR （03KA1831）、作为GAMRIF一部分的英国DHSC、日本MHLW、荷兰卫生、福利和体育部和国际合作总局、瑞士联邦公共卫生办公室、瑞士日内瓦州和Örebro瑞典大学医院的赠款。
{"title":"Microbiological analysis and whole-genome sequencing of Neisseria gonorrhoeae from the microbiological failures in the international, zoliflodacin, phase 3, clinical trial for treatment of uncomplicated urogenital gonorrhoea: a retrospective, genomic, observational study","authors":"Prof Magnus Unemo PhD , Daniel Golparian MSc , Varalakshmi Elango MD , Esther Bettiol MD , Prof Laura J V Piddock PhD , Subasree Srinivasan MD , Patricia A Bradford PhD , Samir H Moussa PhD , Sarah M McLeod PhD , John P Mueller PhD , Prof Edward W Hook III MD , Alison Luckey MD","doi":"10.1016/j.lanmic.2025.101270","DOIUrl":"10.1016/j.lanmic.2025.101270","url":null,"abstract":"<div><h3>Background</h3><div>Zoliflodacin, a first-in-class oral bacterial, DNA gyrase (GyrB) inhibitor, showed non-inferiority to ceftriaxone combined with azithromycin in a recent large international, phase 3, randomised controlled trial for treatment of uncomplicated urogenital gonorrhoea. The aim of this study was to describe the microbiological and whole-genome sequencing (WGS) analyses of paired baseline (pre-treatment) and test-of-cure (TOC) gonococcal isolates from the zoliflodacin phase 3, randomised controlled trial to further characterise and evaluate the protocol-specified microbiological failures with zoliflodacin (n=22) or ceftriaxone and azithromycin (n=1).</div></div><div><h3>Methods</h3><div>In this retrospective, genomic, observational study, results from antimicrobial susceptibility testing (agar dilution method) of isolates (n=960; 936 baseline isolates from 763 participants and 24 TOC isolates [23 with a paired baseline isolate in the same anatomical site] from 20 participants) collected during the zoliflodacin phase 3, randomised controlled trial done in 16 outpatient clinics in Belgium, the Netherlands, South Africa, Thailand, and the USA (Nov 6, 2019–March 16, 2023) are described. WGS analysis was performed on paired baseline and TOC isolates from participants with microbiological failures (zoliflodacin 44 isolates [19 participants]; ceftriaxone and azithromycin two isolates [one participant]), and the three baseline isolates with highest zoliflodacin minimum inhibitory concentration (MIC 0·5 mg/L).</div></div><div><h3>Findings</h3><div>All isolates were inhibited by the same zoliflodacin concentrations (MICs ≤0·008 to 0·5 mg/L) as wild-type strains cultured internationally in 2013–23. In participants with a microbiological failure after zoliflodacin treatment (n=22, 19 participants), zoliflodacin MIC values for baseline and TOC isolates were similar, and resistance selection was lacking. WGS showed that five (23%) of 22 infections (95% CI 10–43 [in four participants]) of zoliflodacin microbiological failures had different strains at TOC versus baseline. In 17 zoliflodacin microbiological failures (15 participants), isolates at baseline and TOC were indistinguishable. 13 of these 17 microbiological failures, corresponding to 59% (95% CI 39–77; 13 of 22) of all zoliflodacin microbiological failures, were in urogenital or rectal sites in 11 participants and the isolates had zoliflodacin MICs less than or equal to 0·008 to 0·25 mg/L. The single microbiological failure after ceftriaxone and azithromycin treatment had different strains at TOC versus at baseline. No sequenced isolates had mutations associated with elevated zoliflodacin MICs.</div></div><div><h3>Interpretation</h3><div>In the zoliflodacin phase 3, randomised controlled trial, 23% of the zoliflodacin microbiological failures and the single ceftriaxone and azithromycin microbiological failure had different gonococcal strains at TOC versus baseline, which suggests r","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 2","pages":"Article 101270"},"PeriodicalIF":20.4,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2026-01-13DOI: 10.1016/j.lanmic.2025.101265
Caroline J Duncombe PhD , Dianna E B Hergott PhD , Weston Staubus MS , Mirte Balke-Buijs MS , Prof James G Kublin MD MPH , Patrick E Duffy MD , Sara A Healy MD , Angela Talley MD , Lisa Jackson MD, MPH , B Kim Lee Sim PhD , Stephen L Hoffman MD , Prof Robert W Sauerwein MD , Prof Meta Roestenberg MD , Prof Sean C Murphy MD PhD
<div><h3>Background</h3><div>Before infecting red blood cells and causing the clinical manifestations of malaria, the hepatotropic parasite <em>Plasmodium falciparum</em> completes a complex liver stage. Sex-based differences in pathogenesis by hepatotropic micro-organisms are well documented but unstudied for <em>P falciparum</em> in humans. We aimed to evaluate the effect of sex on the time to blood-stage positivity and initial blood-stage parasite densities as indicators of liver-stage dynamics and parasite replication.</div></div><div><h3>Methods</h3><div>We conducted a pooled analysis of data from malaria-naive participants in control groups from controlled human malaria infection (CHMI) studies conducted between Jan 1, 2010, and Dec 31, 2024, in which samples were tested using <em>Plasmodium</em> 18S ribosomal RNA nucleic acid amplification tests (18S NAATs) at laboratories in Seattle (WA, USA) and Leiden (Netherlands). Participants aged 18–48 years were eligible for inclusion if they were in placebo or infectivity control groups in any CHMI study at the two laboratories and developed parasitaemia following CHMI. Patient demographics and 18S NAAT data were obtained from study leads at each centre and collated, standardised, and reviewed. Information on <em>P falciparum</em> strain, challenge route, and sampling schedule were extracted from study protocols or publications. The main outcome, time to positivity (TTP), was calculated as the study day of the first positive 18S NAAT of any density, measured during a 28-day monitoring period following CHMI. Using an interval-censored generalised gamma accelerated failure time model, we compared time to blood-stage positivity by sex, adjusting for challenge route, <em>P falciparum</em> strain, and study site. Odds of developing detectable infection after 7 days post-challenge was compared between male and female participants using a linear mixed-effects model adjusted for the same terms.</div></div><div><h3>Findings</h3><div>Evaluable data were available from 102 control participants (48 [47%] female and 54 [53%] male) across 13 CHMI studies. There was moderate heterogeneity between studies (<em>I</em><sup>2</sup>=31% [95% CI 0–57]). There were no notable demographic differences between male and female participants regarding age, challenge route, or strain. The mean time to first detectable parasitaemia was slightly longer in male participants (7·59 days [SD 1·15]) than in female participants (7·17 days [0·91]). Adjusted accelerated failure time analysis suggested that TTP occurred 8% later in male participants than female participants (time ratio 1·08 [1·03–1·16]). Male participants were significantly more likely than female participants to have a detectable infection after day 7 (19 [35%] of 54 male participants <em>vs</em> six [13%] of 48 female participants), with adjusted odds of delayed infection 5·20 times (95% CI 1·52–17·70) higher in male than female participants.</div></div><div><h3>Inter
背景：嗜肝性寄生虫恶性疟原虫（Plasmodium falciparum）在感染红细胞并引起疟疾临床表现之前，完成了复杂的肝期。嗜肝微生物在人类恶性疟原虫发病机制上的性别差异已得到充分记录，但尚未研究。我们的目的是评估性别对血期阳性时间和初始血期寄生虫密度的影响，作为肝期动态和寄生虫复制的指标。方法：我们对2010年1月1日至2024年12月31日在美国西雅图（WA， USA）和荷兰莱顿（Leiden）的实验室进行的控制性人疟疾感染（CHMI）研究中未患疟疾的对照组参与者的数据进行了汇总分析，其中样本使用疟原虫18S核糖体RNA核酸扩增试验（18S NAATs）进行了检测。年龄在18-48岁的参与者，如果他们在两个实验室的任何CHMI研究中处于安慰剂组或感染性对照组，并且在CHMI后出现寄生虫病，则有资格纳入。患者人口统计数据和18S NAAT数据从每个中心的研究线索中获得，并进行整理、标准化和审查。关于恶性疟原虫毒株、攻毒途径和采样计划的信息从研究方案或出版物中提取。在CHMI后的28天监测期间，以首次出现任何密度的18S NAAT阳性的研究天数为主要结果，即到达阳性时间（TTP）。使用间隔剔除广义伽玛加速失效时间模型，我们按性别比较时间与血期阳性，调整攻毒途径、恶性疟原虫品系和研究地点。使用线性混合效应模型对相同条件进行调整，比较了男性和女性参与者在攻击后7天发生可检测感染的几率。研究结果：在13项CHMI研究中，102名对照受试者（48名[47%]女性，54名[53%]男性）获得了可评估的数据。研究间存在中等异质性（I2=31% [95% CI 0-57]）。男性和女性参与者在年龄、挑战路线或压力方面没有显著的人口统计学差异。男性受试者首次检测到寄生虫病的平均时间（7.59 d [SD 1.15]）略长于女性受试者（7.17 d[0.91]）。校正加速失效时间分析表明，男性受试者TTP发生时间比女性受试者晚8%（时间比为1.08[1.03 -1·16]）。在第7天之后，男性参与者比女性参与者更有可能出现可检测到的感染（54名男性参与者中有19人[35%]对48名女性参与者中有6人[13%]），男性延迟感染的调整几率比女性参与者高5.20倍（95% CI 1.52 - 17.70）。解释：我们的研究结果表明，与女性个体相比，男性个体更有可能在CHMI合并恶性疟原虫后延迟检测到血期寄生虫。虽然不能直接测量肝期负荷是一个限制，但CHMI提供了一个受控的系统来推断肝期动力学。因此，恶性疟原虫感染可能涉及肝脏中性别特异性宿主-病原体相互作用，强调了在肝脏靶向临床干预中将性别作为生物学变量考虑的重要性。资助：盖茨基金会和华盛顿大学。
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Pub Date : 2026-02-01Epub Date: 2025-09-09DOI: 10.1016/j.lanmic.2025.101235
Maroun M Sfeir
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Pub Date : 2026-02-01Epub Date: 2026-02-05DOI: 10.1016/j.lanmic.2025.101264
Max Alexander Bär PhD , Nadège Akissi Kouamé MSc , Sadikou Touré , Jean Tenena Coulibaly PhD , Pierre Henri Hermann Schneeberger PhD , Prof Jennifer Keiser PhD
<div><h3>Background</h3><div>Trichuriasis is a neglected tropical disease that affects up to 500 million individuals and can cause considerable morbidity. For decades, trichuriasis was thought to be caused by one species of whipworm, <em>Trichuris trichiura</em>. The aim of this study was to investigate the origin of differences in response rates to the best available anthelmintic treatment for trichuriasis—a combination of albendazole and ivermectin—in Côte d’Ivoire by analysing the parasite population.</div></div><div><h3>Methods</h3><div>In this morphological, genomic, and genome-wide association study (GWAS) with drug sensitivity we used long-read and short-read sequencing approaches and assembled a high-quality reference genome of <em>Trichuris incognita</em> n sp isolated in a primary interventional study conducted in the Lagunes district of Côte d’Ivoire. Children aged 6–12 years were screened between July 14, 2022, and July 31, 2022; children positive for <em>T trichiura</em> on duplicate Kato–Katz smears and with infection intensity of 200 eggs per gram or more were eligible and treated first with albendazole (400 mg) and ivermectin (200 μg/kg) then with oxantel pamoate (20 mg/kg). We constructed a species tree of the <em>Trichuris</em> genus using 12 434 orthologous groups. We sequenced individual worms, which were used to confirm the phylogenetic placement and investigate patterns of adaptation through comparative genomic analyses. Finally, we conducted a GWAS to compare albendazole–ivermectin sensitive worms to drug non-sensitive worms.</div></div><div><h3>Findings</h3><div>670 children were screened, of whom 243 were enrolled and from whom 271 worms were isolated after the first treatment and 827 worms after the second treatment. Sufficient DNA was recovered from 747 worms of which 721 were suitable for further bioinformatic analysis; of these, 179 were albendazole–ivermectin sensitive worms and 542 were drug non-sensitive worms. We present and characterise a new, human-infecting <em>Trichuris</em> species named <em>T incognita</em> n sp, which is morphologically indistinguishable from <em>T trichiura</em>, but forms a distinct phylogenetic clade, closer to <em>Trichuris suis</em> than to the canonical human-infective <em>T trichiura</em>. Comparative genomic analysis of genes suspected to confer resistance to either albendazole or ivermectin in helminths revealed a high number of <em>β-tubulin</em> orthologs, present in the whole population of <em>T incognita</em> n sp, compared with the canonical <em>T trichiura</em> species, but these genes were not associated with a resistant phenotype. The GWAS did not provide conclusive evidence of adaptation to drug pressure within the same species.</div></div><div><h3>Interpretation</h3><div>Our results demonstrate that trichuriasis can be caused by multiple whipworm species, and that differences in response rates might result from species responding differently to drug treatment, rather than
背景：鞭虫病是一种被忽视的热带疾病，影响多达5亿人，可引起相当高的发病率。几十年来，人们一直认为鞭虫病是由一种鞭虫引起的。这项研究的目的是通过分析科特迪瓦Côte的寄生虫种群，来调查对血吸虫病的最佳驱虫药治疗（阿苯达唑和伊维菌素的联合治疗）反应率差异的来源。方法：在这项与药物敏感性的形态学、基因组学和全基因组关联研究（GWAS）中，我们使用长读和短读测序方法，组装了在Côte科特迪瓦Lagunes地区进行的初级介入研究中分离到的Trichuris incognita n sp的高质量参考基因组。在2022年7月14日至7月31日期间对6-12岁儿童进行筛查；重复Kato-Katz涂片阳性且感染强度≥200个鸡蛋/克的儿童符合条件，先用阿苯达唑（400 mg）和伊维菌素（200 μg/kg）治疗，然后用帕莫酸牛胺特（20 mg/kg）治疗。我们利用12 434个同源类群构建了一个毛缕属的种树。我们对单个蠕虫进行了测序，用于确认系统发育位置，并通过比较基因组分析研究适应模式。最后，我们进行了GWAS比较阿苯达唑-伊维菌素敏感的蠕虫和药物不敏感的蠕虫。结果：筛选了670名儿童，其中243名入组，在第一次治疗后分离出271条蠕虫，在第二次治疗后分离出827条蠕虫。从747只蠕虫中提取了足够的DNA，其中721只适合进一步的生物信息学分析；其中，阿苯达唑-伊维菌素敏感虫179只，药物不敏感虫542只。我们提出并描述了一种新的，人类感染的毛滴虫物种，命名为incognita n sp，它在形态上与毛滴虫难以区分，但形成了一个独特的系统发育分支，更接近于猪毛滴虫，而不是典型的人类感染的毛滴虫。对蛔虫对阿苯达唑或伊维菌素产生抗性的基因进行了比较基因组分析，结果显示，与典型的毛线虫物种相比，在整个蠕虫种群中存在大量β-微管蛋白同源基因，但这些基因与抗性表型无关。GWAS没有提供在同一物种内适应药物压力的确凿证据。解释：我们的研究结果表明，鞭虫病可以由多种鞭虫引起，反应率的差异可能是由于不同物种对药物治疗的反应不同，而不是由于种内抗性的建立。这一发现，加上对阿苯达唑-伊维菌素的高度耐受性，标志着我们如何理解和处理鞭虫感染的重大转变。资助：欧洲研究委员会。
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Pub Date : 2026-02-01Epub Date: 2025-09-23DOI: 10.1016/j.lanmic.2025.101247
Francesco Maria Galassi , Mauro Vaccarezza , Marco Vitale , Elena Varotto
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