Discovery of a novel albendazole-ivermectin refractory Trichuris species, T. hominis, in Côte d’Ivoire patients through fecal DNA metabarcoding

Albendazole-ivermectin combination therapy is a promising alternative to benzimidazole monotherapy for Trichuris trichiura control. We used fecal DNA metabarcoding to genetically characterize Trichuris populations in patients from a clinical trial showing lower albendazole-ivermectin efficacy in Côte d’Ivoire (ERR below 70%) than in Lao PDR and Tanzania (ERR above 98%). ITS-1 and ITS-2 rDNA metabarcoding revealed the entire Côte d’Ivoire Trichuris population was phylogenetically distinct from T. trichiura in Lao PDR and Tanzania, and more closely related to the porcine parasite Trichuris suis. Complete mitogenomes of eight adult Trichuris from Côte d’Ivoire confirmed their species-level differentiation. Corresponding Trichuris ITS-1 and ITS-2 sequences in NCBI from individual human patients in Cameroon and Uganda and three captive non-human primates suggest this newly recognized species, T. hominis, is distributed beyond Côte d’Ivoire and has zoonotic potential. Further work is needed to assess the impact of this Trichuris species on soil transmitted helminth control programs.

[1]  J. Coulibaly,et al.  Genetic makeup of Trichuris hominis, a novel Trichuris species naturally infecting humans and displaying signs of resistance to drug treatment , 2024, bioRxiv.

[2]  J. Keiser,et al.  Efficacy and safety of co-administered ivermectin and albendazole in school-aged children and adults infected with Trichuris trichiura in Côte d'Ivoire, Laos, and Pemba Island, Tanzania: a double-blind, parallel-group, phase 3, randomised controlled trial , 2021, The Lancet Infectious Diseases.

[3]  M. Berriman,et al.  Population genomics of ancient and modern Trichuris trichiura , 2021, Nature Communications.

[4]  E. Redman,et al.  Multiple drug resistance in hookworms infecting greyhound dogs in the USA , 2021, bioRxiv.

[5]  R. Callejón,et al.  Trichuris trichiura (Linnaeus, 1771) From Human and Non-human Primates: Morphology, Biometry, Host Specificity, Molecular Characterization, and Phylogeny , 2021, Frontiers in Veterinary Science.

[6]  J. Utzinger,et al.  The global progress of soil-transmitted helminthiases control in 2020 and World Health Organization targets for 2030 , 2020, PLoS neglected tropical diseases.

[7]  Olga Chernomor,et al.  IQ-TREE 2: New Models and Efficient Methods for Phylogenetic Inference in the Genomic Era , 2019, bioRxiv.

[8]  E. P. Medici,et al.  Phylogenetics, patterns of genetic variation and population dynamics of Trypanosoma terrestris support both coevolution and ecological host-fitting as processes driving trypanosome evolution , 2019, Parasites & Vectors.

[9]  G. Weil,et al.  Update on the current status of onchocerciasis in Côte d’Ivoire following 40 years of intervention: Progress and challenges , 2018, PLoS neglected tropical diseases.

[10]  E. Hoberg,et al.  Genetic characterisation and phylogenetic status of whipworms (Trichuris spp.) from captive non-human primates in China, determined by nuclear and mitochondrial sequencing , 2018, Parasites & Vectors.

[11]  S. Knopp,et al.  Efficacy and safety of co-administered ivermectin plus albendazole for treating soil-transmitted helminths: A systematic review, meta-analysis and individual patient data analysis , 2018, PLoS neglected tropical diseases.

[12]  Wen-Bin Yu,et al.  GetOrganelle: a fast and versatile toolkit for accurate de novo assembly of organelle genomes , 2018, Genome Biology.

[13]  Jia Gu,et al.  fastp: an ultra-fast all-in-one FASTQ preprocessor , 2018, bioRxiv.

[14]  J. Keiser,et al.  Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis , 2017, British Medical Journal.

[15]  Y. Djuardi,et al.  Improved diagnosis of Trichuris trichiura by using a bead-beating procedure on ethanol preserved stool samples prior to DNA isolation and the performance of multiplex real-time PCR for intestinal parasites , 2017, Parasitology.

[16]  Paul J. McMurdie,et al.  DADA2: High resolution sample inference from Illumina amplicon data , 2016, Nature Methods.

[17]  J. Wasmuth,et al.  Exploring the Gastrointestinal “Nemabiome”: Deep Amplicon Sequencing to Quantify the Species Composition of Parasitic Nematode Communities , 2015, PloS one.

[18]  P. Nejsum,et al.  Human Trichuriasis: Whipworm Genetics, Phylogeny, Transmission and Future Research Directions , 2015, Current Tropical Medicine Reports.

[19]  R. Gasser,et al.  Mitochondrial Genome Analyses Suggest Multiple Trichuris Species in Humans, Baboons, and Pigs from Different Geographical Regions , 2015, PLoS neglected tropical diseases.

[20]  S. Cavallero,et al.  Genetic heterogeneity and phylogeny of Trichuris spp. from captive non-human primates based on ribosomal DNA sequence data. , 2015, Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases.

[21]  T. Goldberg,et al.  Hidden Population Structure and Cross-species Transmission of Whipworms (Trichuris sp.) in Humans and Non-human Primates in Uganda , 2014, PLoS neglected tropical diseases.

[22]  C. R. Stensvold,et al.  Molecular Testing for Clinical Diagnosis and Epidemiological Investigations of Intestinal Parasitic Infections , 2014, Clinical Microbiology Reviews.

[23]  S. Brooker,et al.  Global numbers of infection and disease burden of soil transmitted helminth infections in 2010 , 2014, Parasites & Vectors.

[24]  P. Nejsum,et al.  Genetic variations in the beta-tubulin gene and the internal transcribed spacer 2 region of Trichuris species from man and baboons , 2013, Parasites & Vectors.

[25]  L. Rinaldi,et al.  Discrimination of Gastrointestinal Nematode Eggs from Crude Fecal Egg Preparations by Inhibitor-Resistant Conventional and Real-Time PCR , 2013, PloS one.

[26]  P. Nejsum,et al.  Is Supplementary Bead Beating for DNA Extraction from Nematode Eggs by Use of the NucliSENS easyMag Protocol Necessary? , 2013, Journal of Clinical Microbiology.

[27]  K. Katoh,et al.  MAFFT Multiple Sequence Alignment Software Version 7: Improvements in Performance and Usability , 2013, Molecular biology and evolution.

[28]  Shihab U. Sobuz,et al.  A Laboratory-Developed TaqMan Array Card for Simultaneous Detection of 19 Enteropathogens , 2012, Journal of Clinical Microbiology.

[29]  M. O'Riain,et al.  Phylogenetic Evidence That Two Distinct Trichuris Genotypes Infect both Humans and Non-Human Primates , 2012, PloS one.

[30]  Marcel Martin Cutadapt removes adapter sequences from high-throughput sequencing reads , 2011 .

[31]  J. Utzinger,et al.  Albendazole and mebendazole administered alone or in combination with ivermectin against Trichuris trichiura: a randomized controlled trial. , 2010, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[32]  Pedro M. Valero-Mora,et al.  ggplot2: Elegant Graphics for Data Analysis , 2010 .

[33]  L. Excoffier,et al.  Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows , 2010, Molecular ecology resources.

[34]  E. Paradis pegas: an R package for population genetics with an integrated-modular approach , 2010, Bioinform..

[35]  S. Brooker,et al.  Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm , 2006, The Lancet.

[36]  P. Shannon,et al.  Cytoscape: a software environment for integrated models of biomolecular interaction networks. , 2003, Genome research.

[37]  M. Ismail,et al.  Efficacy of albendazole and its combinations with ivermectin or diethylcarbamazine (DEC) in the treatment of Trichuris trichiura infections in Sri Lanka. , 1999, Annals of tropical medicine and parasitology.

[38]  S. Nadler,et al.  Phylogenetic trees support the coevolution of parasites and their hosts , 1988, Nature.

[39]  P. Legendre,et al.  vegan : Community Ecology Package. R package version 1.8-5 , 2007 .

[40]  V. Belizario,et al.  A comparison of the efficacy of single doses of albendazole, ivermectin, and diethylcarbamazine alone or in combinations against Ascaris and Trichuris spp. , 2003, Bulletin of the World Health Organization.