Journal Articles
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Item 20 years later: unravelling the genomic success of New Zealand’s home-grown AK3 community-associated methicillin-resistant Staphylococcus aureus(Microbiology Society, 2025-07-25) White RT; Bakker S; Bloomfield M; Burton M; Elvy J; Eustace A; French NP; Grant J; Greening SS; Grinberg A; Harland C; Hutton S; Karkaba A; Martin J; Matthews B; Miller H; Straub C; Tarring C; Taylor WT; Ussher J; Velasco C; Voss EM; Dyet KMethicillin-resistant Staphylococcus aureus (MRSA) represents a significant public health challenge. In New Zealand, the community-associated MRSA sequence type (ST)5, carrying the staphylococcal cassette chromosome mec (SCCmec) type IV genetic element (which confers methicillin resistance), has been predominant since its detection in 2005. Known informally as the AK3 strain, it also exhibits resistance to fusidic acid. Here, we investigated the genomic evolution of the AK3 strain by analysing 397 genomes, comprising 361 MRSA and 36 closely related methicillin-susceptible S. aureus (MSSA) genomes, including 285 recently sequenced isolates from New Zealand spanning 2020 (n=30), 2021 (n=77), 2022 (n=88), 2023 (n=73) and 2024 (n=17). Phylogenetic analysis revealed that the AK3 strain evolved through stepwise acquisition of mobile genetic elements, with an MSSA ancestor likely introduced to New Zealand in the late 1970s. The lineage first acquired a SaPITokyo12571-like pathogenicity island, which contains the staphylococcal enterotoxin C bovine variant (sec-bov) and an enterotoxin-like protein (sel), between 1984 and 1991. This was followed by the integration of SCCmec type IV and adjacent fusidic acid resistance operon between 1997 and 2000. This timing coincides with increased community fusidic acid use in New Zealand. The AK3 strain then diversified into three major clades, spreading throughout New Zealand and Australia, with sporadic detection in European countries and Samoa. Our findings demonstrate how the sequential acquisition of mobile genetic elements, combined with antibiotic selection pressure, likely contributed to the successful emergence of AK3 and its spread in the South Pacific region.Item Evidence for a Role of Extraintestinal Pathogenic Escherichia coli, Enterococcus faecalis and Streptococcus gallolyticus in the Aetiology of Exudative Cloacitis in the Critically Endangered Kākāpō (Strigops habroptilus)(John Wiley and Sons Ltd, 2025-04-19) French RK; Waller SJ; Wierenga JR; Grimwood RM; Hodgkinson-Bean J; Digby A; Uddstrom L; Eason D; Kākāpō Recovery Team; Argilla LS; Biggs PJ; Cookson A; French NP; Geoghegan JLThe kākāpō is a critically endangered flightless parrot which suffers from exudative cloacitis, a debilitating disease resulting in inflammation of the vent margin or cloaca. Despite this disease emerging over 20 years ago, the cause of exudative cloacitis remains elusive. We used total RNA sequencing and metatranscriptomic analysis to characterise the infectome of lesions and cloacal swabs from nine kākāpō affected with exudative cloacitis, and compared this to cloacal swabs from 45 non-diseased kākāpō. We identified three bacterial species—Streptococcus gallolyticus, Enterococcus faecalis and Escherichia coli—as significantly more abundant in diseased kākāpō compared to healthy individuals. The genetic diversity observed in both S. gallolyticus and E. faecalis among diseased kākāpō suggests that these bacteria originate from exogenous sources rather than from kākāpō-to-kākāpō transmission. The presence of extraintestinal pathogenic E. coli (ExPEC)-associated virulence factors in the diseased kākāpō population suggests that E. coli may play a critical role in disease progression by facilitating iron acquisition and causing DNA damage in host cells, possibly in association with E. faecalis. No avian viral, fungal nor other parasitic species were identified. These results, combined with the consistent presence of one E. coli gnd sequence type across multiple diseased birds, suggest that this species may be the primary cause of exudative cloacitis. These findings shed light on possible causative agents of exudative cloacitis, and offer insights into the interplay of microbial factors influencing the disease.Item Transmission pathways of Campylobacter jejuni between humans and livestock in rural Ethiopia are highly complex and interdependent(BioMed Central Limited, London, United Kingdom, 2025-12-01) Singh N; Thystrup CAN; Hassen BM; Bhandari M; Rajashekara G; Hald TM; Manary MJ; McKune SL; Hassen JY; Smith HL; Marshall JC; French NP; Havelaar AH; Mekuria ZH; Weldesenbet YD; Yang Y; Li X; Gebreyes W; Shaikh N; Bhrane M; Dawid MM; Usmail MM; Deblais L; Mechlowitz K; Umer KA; Roba KT; Hassen KA; Amin JK; Usmane IA; Ahmed IA; Yimer G; Yusuf EA; Chen D; Saleem C; Ahmedo BU; Ojeda AE; Ibrahim AM; Seran AJBackground: Campylobacter jejuni and C. coli are the most common causes of bacterial enteritis worldwide whereas symptomatic and asymptomatic infections are associated with stunting in children in low- and middle-income countries. Little is known about their sources and transmission pathways in low- and middle-income countries, and particularly for infants and young children. We assessed the genomic diversity of C. jejuni in Eastern Ethiopia to determine the attribution of infections in infants under 1 year of age to livestock (chickens, cattle, goats and sheep) and other humans (siblings, mothers). Results: Among 287 C. jejuni isolates, 48 seven-gene sequence types (STs), including 11 previously unreported STs were identified. Within an ST, the core genome STs of multiple isolates differed in fewer than five alleles. Many of these isolates do not belong to the most common STs reported in high-resource settings, and of the six most common global STs, only ST50 was found in our study area. Isolates from the same infant sample were closely related, while those from consecutive infant samples often displayed different STs, suggesting rapid clearance and new infection. Four different attribution models using different genomic profiling methods, assumptions and estimation methods predicted that chickens are the primary reservoir for infant infections. Infections from chickens are transmitted with or without other humans (mothers, siblings) as intermediate sources. Model predictions differed in terms of the relative importance of cattle versus small ruminants as additional sources. Conclusions: The transmission pathways of C. jejuni in our study area are highly complex and interdependent. While chickens are the most important reservoir of C. jejuni, ruminant reservoirs also contribute to the infections. The currently nonculturable species Candidatus C. infans is also highly prevalent in infants and is likely anthroponotic. Efforts to reduce the colonization of infants with Campylobacter and ultimately stunting in low-resource settings are best aimed at protecting proximate sources such as caretakers’ hands, food and indoor soil through tight integration of the currently siloed domains of nutrition, food safety and water, sanitation and hygiene.Item Zoonotic transmission of asymptomatic carriage Staphylococcus aureus on dairy farms in Canterbury, New Zealand.(Microbiology Society, 2024-12-04) Straub C; Taylor W; French NP; Murdoch DR; Priest P; Anderson T; Scott PZoonotic pathogen transmission is of growing concern globally, with agricultural intensification facilitating interactions between humans, livestock and wild animals. Staphylococcus aureus is a major human pathogen, but it also causes mastitis in dairy cattle, leading to an economic burden on the dairy industry. Here, we investigated transmission within and between cattle and humans, including potential zoonotic transmission of S. aureus isolated from cattle and humans from three dairy farms and an associated primary school in New Zealand. Nasal swabs (N=170) were taken from healthy humans. Inguinal and combined nasal/inguinal swabs were taken from healthy cattle (N=1163). Whole-genome sequencing was performed for 96 S. aureus isolates (44 human and 52 cattle). Multilocus sequence typing and assessments of antimicrobial resistance and virulence were carried out. Potential within- and across-species transmission events were determined based on single nucleotide polymorphisms (SNPs). Thirteen potential transmission clusters were detected, with 12 clusters restricted to within-species and one potential zoonotic transmission cluster (ST5). Potential transmission among cattle was mostly limited to single age groups, likely because different age groups are managed separately on farms. While the prevalence of antimicrobial resistance (AMR) was low among both bovine and human isolates, the discovery of an extended-spectrum beta-lactamase gene (bla TEM-116) in a bovine isolate was concerning. This study provides evidence around frequency and patterns of potential transmission of S. aureus on dairy farms and highlights the AMR and virulence profile of asymptomatic carriage S. aureus isolates.Item Preparing for the next pandemic: insights from Aotearoa New Zealand's Covid-19 response(Elsevier Ltd, 2025-03-18) French NP; Maxwell H; Baker MG; Callaghan F; Dyet K; Geoghegan JL; Hayman DTS; Huang QS; Kvalsvig A; Russell E; Scott P; Thompson TP; Plank MJIn 2020 Aotearoa New Zealand, like many other countries, faced the coronavirus pandemic armed with an influenza-based pandemic plan. The country adapted rapidly to mount a highly strategic and effective elimination response to the SARS-CoV-2 pandemic. However, implementation was hampered by gaps in pandemic preparedness. These gaps undermined effectiveness of the response and exacerbated inequitable impacts of both Covid-19 disease and control measures. Our review examines the Covid-19 response, reflecting on strengths, limitations and implications for pandemic planning. We identify three key areas for improvement: 1) development of a systematised procedure for risk assessment of a new pandemic pathogen; 2) investment in essential capabilities during inter-pandemic periods; and 3) building equity into all stages of the response. We present a typology of potential pathogens and scenarios and describe the evidence assessment process and core capabilities required for countries to respond fluidly, equitably, and effectively to a rapidly emerging pandemic threat.Item Campylobacter colonization and undernutrition in infants in rural eastern Ethiopia - a longitudinal community-based birth cohort study.(Frontiers Media S.A., 2025-01-07) Chen D; McKune SL; Yang Y; Usmane IA; Ahmed IA; Amin JK; Ibrahim AM; Seran AJ; Shaik N; Ojeda A; Hassen BM; Deblais L; Ahmedo BU; Hassen KA; Bhrane M; Li X; Singh N; Roba KT; French NP; Rajashekara G; Manary MJ; Hassen JY; Havelaar AH; CAGED Research TeamBackground: Campylobacter is associated with environmental enteric dysfunction (EED) and malnutrition in children. Campylobacter infection could be a linchpin between livestock fecal exposure and health outcomes in low-resource smallholder settings. Methods: We followed a birth cohort of 106 infants in rural smallholder households in eastern Ethiopia up to 13 months of age. We measured anthropometry, surveyed sociodemographic determinants, and collected stool and urine samples. A short survey was conducted during monthly visits, infant stool samples were collected, and Campylobacter spp. was quantified using genus-specific qPCR. In month 13, we collected stool and urine samples to assay for EED biomarkers. We employed regression analyses to assess the associations of household determinants with Campylobacter colonization, EED, and growth faltering. Results: The Campylobacter load in infant stools increased with age. The mean length-for-age Z-score (LAZ) decreased from −0.45 at 3–4 months of age to −2.06 at 13 months, while the prevalence of stunting increased from 3 to 51%. The prevalence of EED at 13 months of age was 56%. A higher Campylobacter load was associated with more frequent diarrhea. Prelacteal feeding significantly increased Campylobacter load in the first month of life. Over the whole follow-up period, Campylobacter load was increased by keeping chickens unconfined at home and unsanitary disposal of infant stools while decreased by mothers’ handwashing with soap. Longitudinally, Campylobacter load was positively associated with food insecurity, introduction of complementary foods, and raw milk consumption. There were no significant associations between Campylobacter load, EED, and LAZ. Conclusion: This study found that most determinants associated with increased Campylobacter infection were related to suboptimal feeding practices and hygiene. The findings related to livestock-associated risks were inconclusive. Although stunting, EED, and Campylobacter prevalence rates all increased to high levels by the end of the first year of life, no significant association between them was identified. While additional research is needed to investigate whether findings from this study are replicable in other populations, community efforts to improve infant and young child feeding practices and food hygiene, and water, sanitation, and hygiene (WaSH) at the household level, could reduce (cross-)contamination at the point of exposure.Item Metabarcoding captures genetic diversity and links cases in outbreaks of cryptosporidiosis in New Zealand.(Elsevier Ltd on behalf of The British Infection Association, 2025-01-30) Ogbuigwe P; Biggs PJ; Garcia-Ramirez JC; Knox MA; Pita A; Velathanthir N; French NP; Hayman DTSCryptosporidiosis is a disease caused by the parasite Cryptosporidium. Globally, it is a leading cause of diarrhoea and a notifiable disease in New Zealand. Molecular analyses of Cryptosporidium isolated from notified cases do not always provide support for epidemiological links between individuals. We hypothesised this could be due to undetected diversity and the use of consensus Sanger sequence analyses. Here, we analysed 105 Cryptosporidium samples from outbreaks and sporadic cases occurring between 2010 and 2018 in New Zealand using both Next-Generation Sequencing (NGS) and Sanger sequencing of the glycoprotein 60 (gp60) locus. NGS metabarcoding at the gp60 locus uncovered significant intra- and inter-sample genotypic diversity in outbreaks and identified subtypes shared by epidemiologically linked cases, along with rare subtypes, suggesting it may be a useful tool for epidemiological investigations.Item Out of (the) bag—encoding categorical predictors impacts out-of-bag samples(PeerJ Inc., 2024-01-01) Smith HL; Biggs PJ; French NP; Smith ANH; Marshall JC; Aleem MPerformance of random forest classification models is often assessed and interpreted using out-of-bag (OOB) samples. Observations which are OOB when a tree is trained may serve as a test set for that tree and predictions from the OOB observations used to calculate OOB error and variable importance measures (VIM). OOB errors are popular because they are fast to compute and, for large samples, are a good estimate of the true prediction error. In this study, we investigate how target-based vs. target-agnostic encoding of categorical predictor variables for random forest can bias performance measures based on OOB samples. We show that, when categorical variables are encoded using a target-based encoding method, and when the encoding takes place prior to bagging, the OOB sample can underestimate the true misclassification rate, and overestimate variable importance. We recommend using a separate test data set when evaluating variable importance and/or predictive performance of tree based methods that utilise a target-based encoding method.Item Genomic diversity of Campylobacter jejuni and Campylobacter coli isolates recovered from human and poultry in Australia and New Zealand, 2017 to 2019.(Microbiology Society, 2024-11-05) Cribb DM; Biggs PJ; McLure AT; Wallace RL; French NP; Glass K; Kirk MDWe used genomic and epidemiological data to assess and compare the population structure and origins of Campylobacter, a major foodborne pathogen, in two neighbouring countries with strong trade and cultural links, similar poultry production systems and frequent movement of people and food products. The most common sequence types (STs) differed between Australia and New Zealand, with many unique to each country. Over half of all STs were represented by a single isolate. Multidrug-resistant (MDR) genotypes were detected in 0.8% of all samples, with no MDR isolates detected in poultry. Quinolone and tetracycline resistant ST6964 was prevalent in New Zealand (10.6% of C. jejuni). Closely related isolates suggested some similar food sources or contacts. We have shown that there is little genetic overlap in human and poultry STs of Campylobacter between the countries, which highlights that this common foodborne pathogen has domestic origins in Australia and New Zealand.Item Population Structure and Antimicrobial Resistance in Campylobacter jejuni and C. coli Isolated from Humans with Diarrhea and from Poultry, East Africa.(Centers for Disease Control and Prevention, 2024-10) French NP; Thomas KM; Amani NB; Benschop J; Bigogo GM; Cleaveland S; Fayaz A; Hugho EA; Karimuribo ED; Kasagama E; Maganga R; Melubo ML; Midwinter AC; Mmbaga BT; Mosha VV; Mshana FI; Munyua P; Ochieng JB; Rogers L; Sindiyo E; Swai ES; Verani JR; Widdowson M-A; Wilkinson DA; Kazwala RR; Crump JA; Zadoks RNCampylobacteriosis and antimicrobial resistance (AMR) are global public health concerns. Africa is estimated to have the world's highest incidence of campylobacteriosis and a relatively high prevalence of AMR in Campylobacter spp. from humans and animals. Few studies have compared Campylobacter spp. isolated from humans and poultry in Africa using whole-genome sequencing and antimicrobial susceptibility testing. We explored the population structure and AMR of 178 Campylobacter isolates from East Africa, 81 from patients with diarrhea in Kenya and 97 from 56 poultry samples in Tanzania, collected during 2006-2017. Sequence type diversity was high in both poultry and human isolates, with some sequence types in common. The estimated prevalence of multidrug resistance, defined as resistance to >3 antimicrobial classes, was higher in poultry isolates (40.9%, 95% credible interval 23.6%-59.4%) than in human isolates (2.5%, 95% credible interval 0.3%-6.8%), underlining the importance of antimicrobial stewardship in livestock systems.