The recent emergence of a multidrug-resistant yeast, Candida auris, has drawn attention to the closely related species from the Candida haemulonii complex that include C. haemulonii, Candida duobushaemulonii, Candida pseudohaemulonii, and the recently identified Candida vulturna. Here, we used antifungal susceptibility testing and whole-genome sequencing (WGS) to investigate drug resistance and genetic diversity among isolates of C. haemulonii complex from different geographic areas in order to assess population structure and the extent of clonality among strains. Although most isolates of all four species were genetically distinct, we detected evidence of the in-hospital transmission of C. haemulonii and C. duobushaemulonii in one hospital in Panama, indicating that these species are also capable of causing outbreaks in healthcare settings. We also detected evidence of the rising azole resistance among isolates of C. haemulonii and C. duobushaemulonii in Colombia, Panama, and Venezuela linked to substitutions in ERG11 gene as well as amplification of this gene in C. haemulonii in isolates in Colombia suggesting the presence of evolutionary pressure for developing azole resistance in this region. Our results demonstrate that these species need to be monitored as possible causes of outbreaks of invasive infection.

Candida auris has emerged globally as a multidrug-resistant yeast that can spread via nosocomial transmission. An initial phylogenetic study of isolates from Japan, India, Pakistan, South Africa, and Venezuela revealed four populations (clades I, II, III, and IV) corresponding to these geographic regions. Since this description, C. auris has been reported in more than 30 additional countries. To trace this global emergence, we compared the genomes of 304 C. auris isolates from 19 countries on six continents. We found that four predominant clades persist across wide geographic locations. We observed phylogeographic mixing in most clades; clade IV, with isolates mainly from South America, demonstrated the strongest phylogeographic substructure. C. auris isolates from two clades with opposite mating types were detected contemporaneously in a single health care facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 360 years; outbreak-causing clusters from clades I, III, and IV originated 36 to 38 years ago. We observed high rates of antifungal resistance in clade I, including four isolates resistant to all three major classes of antifungals. Mutations that contribute to resistance varied between the clades, with Y132F in ERG11 as the most widespread mutation associated with azole resistance and S639P in FKS1 for echinocandin resistance. Copy number variants in ERG11 predominantly appeared in clade III and were associated with fluconazole resistance. These results provide a global context for the phylogeography, population structure, and mechanisms associated with antifungal resistance in C. auris IMPORTANCE In less than a decade, C. auris has emerged in health care settings worldwide; this species is capable of colonizing skin and causing outbreaks of invasive candidiasis. In contrast to other Candida species, C. auris is unique in its ability to spread via nosocomial transmission and its high rates of drug resistance. As part of the public health response, whole-genome sequencing has played a major role in characterizing transmission dynamics and detecting new C. auris introductions. Through a global collaboration, we assessed genome evolution of isolates of C. auris from 19 countries. Here, we described estimated timing of the expansion of each C. auris clade and of fluconazole resistance, characterized discrete phylogeographic population structure of each clade, and compared genome data to sensitivity measurements to describe how antifungal resistance mechanisms vary across the population. These efforts are critical for a sustained, robust public health response that effectively utilizes molecular epidemiology.

Candida haemulonii is an emerging multidrug-resistant yeast that can cause invasive candidiasis. Here, we report the first genome sequence of C. haemulonii (isolate B11899) generated using PacBio sequencing technology. The estimated genome size was 13.3 Mb, with a GC content of 45.19%.

Health worker experience and community support may be higher in high HIV prevalence regions than low prevalence regions, leading to improved prevention of mother-to-child HIV transmission (PMTCT) programs. We evaluated 6-week and 9-month infant HIV transmission risk (TR) in a high prevalence region and nationally. Population-proportionate-to-size sampling was used to select 141 clinics in Kenya, and mobile teams surveyed mother-infant pairs attending 6-week and 9-month immunizations. HIV DNA testing was performed on HIV-exposed infants. Among 2521 mother-infant pairs surveyed nationally, 2423 (94.7%) reported HIV testing in pregnancy or prior diagnosis, of whom 200 (7.4%) were HIV-infected and 188 infants underwent HIV testing. TR was 8.8% (4.0%-18.3%) in 6-week and 8.9% (3.2%-22.2%) in 9-month cohorts including mothers with HIV diagnosed postpartum, of which 53% of infant infections were due to previously undiagnosed mothers. Of 276 HIV-exposed infants in the Nyanza survey, TR was 1.4% (0.4%-5.3%) at 6-week and 5.1% (2.5%-9.9%) at 9-months. Overall TR was lower in Nyanza, high HIV region, than nationally (3.3% vs. 7.2%, P = 0.02). HIV non-disclosure to male partners and incomplete ARVs were associated with TR in both surveys [aOR = 12.8 (3.0-54.3); aOR = 5.6 (1.2-27.4); aOR = 4.5 (1.0-20.0), aOR = 2.5, (0.8-8.4), respectively]. TR was lower in a high HIV prevalence region which had better ARV completion and partner HIV disclosure, possibly due to programmatic efficiencies or community/peer/partner support. Most 9-month infections were among infants of mothers without prior HIV diagnosis. Strategies to detect incident or undiagnosed maternal infections will be important to achieve PMTCT.

BACKGROUND: Tuberculosis (TB) screening in Prevention of Mother-To-Child Transmission (PMTCT) programs is important to improve TB detection, prevention and treatment. METHODS: As part of a national PMTCT program evaluation, mother-infant pairs attending 6-week and 9-month immunization visits were enrolled at 141 maternal and child health clinics throughout Kenya. Clinics were selected using population-proportion-to-size sampling with oversampling in a high human immunodeficiency virus (HIV) prevalence region. The World Health Organization (WHO) TB symptom screen was administered to HIV-infected mothers, and associations with infant cofactors were determined. RESULTS: Among 498 HIV-infected mothers, 165 (33%) had a positive TB symptom screen. Positive maternal TB symptom screen was associated with prior TB (P = 0.04). Women with a positive TB symptom screen were more likely to have an infant with HIV infection (P = 0.02) and non-specific TB symptoms, including cough (P = 0.003), fever (P = 0.05), and difficulty breathing (P = 0.01). TB exposure was reported by 11% of the women, and 15% of the TB-exposed women received isoniazid preventive therapy. CONCLUSIONS: Postpartum HIV-infected mothers frequently had a positive TB symptom screen. Mothers with a positive TB symptom screen were more likely to have infants with HIV or non-specific TB symptoms. Integration of maternal TB screening and prevention into PMTCT programs may improve maternal and infant outcomes.

BACKGROUND: Rates of pregnancy and HIV infection are high among adolescents. However, their engagement in prevention of mother-to-child HIV transmission (PMTCT) services is poorly characterized. We compared engagement in the PMTCT cascade between adult and adolescent mothers in Kenya. METHODS: We conducted a nationally representative cross-sectional survey of mother-infant pairs attending 120 maternal child health clinics selected by probability-proportionate-to-size-sampling, with a secondary survey oversampling HIV-positive mothers in 30 clinics. ANC attendance, HIV testing and ARV use were compared between adolescent (age ≤19) and adult mothers using Chi-square tests and logistic regression. RESULTS: Among 2521 mothers, 278 (12.8%) were adolescents. Adolescents were less likely than adults to be employed (16.5% vs. 37.9%), married (66.1% vs. 88.3%), have intended pregnancy (40.5% vs. 58.6%), or have disclosed their HIV status (77.5% vs. 90.7%) (p<0.01 for all). Adolescents were less likely than adults to attend ≥4 ANC visits (35.2% vs. 45.6%, p=0.002). This effect remained significant when adjusting for employment, household crowding, pregnancy intention, gravidity and HIV status (aOR[95% CI]=0.54[0.37-0.97], p=0.001). Among 2359 women without previous HIV testing, 96.1% received testing during pregnancy; testing levels did not differ between adolescents and adults. Among 288 HIV-positive women not on ART prior to pregnancy, adolescents were less likely than adults to be on ARVs (65.0% vs. 85.8%, p=0.01) or to have infants on ARVs (85.7% vs. 97.7%, p=0.005). CONCLUSIONS: Adolescent mothers had poorer ANC attendance and uptake of ARVs for PMTCT. Targeted interventions are needed to improve retention of this vulnerable population in the PMTCT cascade.