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.

AbstractCandida 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 over 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 healthcare facility in Kenya. We estimated a Bayesian molecular clock phylogeny and dated the origin of each clade within the last 339 years; outbreak-causing clusters from Clades I, III, and IV originated 34-35 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.ImportanceIn less than a decade, C. auris has emerged in healthcare 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.

SummaryCandida auris is an emerging multidrug-resistant (MDR) fungus associated with invasive infections and high mortality. This report describes 9 patients from whom C. auris was isolated at a hospital in Panama City, Panama, the first such cases in Central America, and highlights the challenges of accurate identification and methods for susceptibility testing. K E Y W O R D Sacurate, Candida auris, diagnose, susceptibility

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Abstract. Chikungunya virus (CHIKV) is a mosquito-borne pathogen that was only endemic in Africa and south Asia until 2005 and, when the virus spread into the Indian Ocean islands, Europe, and Asia. Autochthonous CHIKV transmission in the Caribbean islands was reported in December of 2013. In Panama, two febrile cases were detected in May of 2014: one traveling from Haiti, and the other traveling from the Dominican Republic. After other imported cases were detected, the first autochthonous case was reported in August of the same year. We detected CHIKV viral RNA and isolated the virus from serum samples. The phylogenetic analysis of the two imported isolates and one autochthonous CHIKV isolate indicated that the viruses belong to the Asian lineage in the Caribbean clade and are related to viruses recently identified in Saint Martin island, British Virgin Islands, China, and the Philippines. Although the circulating CHIKV lineages in the Americas have not yet been described, our results suggest that the Asian lineage is circulating in most American countries reporting autochthonous infection.Chikungunya virus (CHIKV; Alphavirus, Togaviridae) is a mosquito-borne pathogen that is endemic in Africa and some countries in Asia. In 2004, a CHIKV epidemic in costal Kenya was reported, and by 2005 and 2006, CHIKV had spread to the Indian Ocean island of La Reunion as well as Asia, where it caused major epidemics. Several imported cases were reported in Europe and the Americas.1 Three mayor lineages of CHIKV have been described: the east, central and south African (ECSA) lineage, the west African lineage, and the Asian lineage.2 A single mutation in the ECSA strain allowed the emergence of the Indian Ocean outbreak lineage (IOL) because of the increase of viral infectivity, dissemination, and transmission of CHIKV in Aedes albopictus.3,4 The IOL has been related to the explosive CHIKV epidemics in the Indian Ocean and Asia and autochthonous infections in Italy and the south of France as well as several imported cases into the Americas.2,5 Therefore, it was believed that the IOL of CHIKV would reach the Americas, 6 where the two vectors Ae. aegypti and Ae. albopictus have an overlapping distribution 7 and adapt to cause autochthonous infection. Autochthonous CHIKV infections caused by the Asian lineage were reported in December of 2013 on the French island of Saint Martin and spread to several others Caribbean islands and Latin American countries in 2014. 8,9 Here, we report the detection of imported cases of CHIKV in Panama and the establishment of autochthonous infections as well as the results of the genetic characterization of the CHIKV viral strains.On May 13 and 14, 2014, two suspected cases of Chikungunya fever were detected in two public medical facilities in Panama City, Panama. The first patient (256114) was a 23-yearold male with the following travel history: Brazil to Haiti to Panama to Brazil. The day before his travel to Haiti from Rio de Janeiro (May 6), he presented fever, myalgia, and general malaise; he ...

31 Dengue virus (DENV) is the most prevalent mosquito-borne virus in the world and a major cause 32 of morbidity in the tropics and subtropics. Upregulation of HLA class I molecules has long been 33 considered a feature of DENV infection, yet this has not been evaluated in the setting of natural 34 infection. Natural killer (NK) cells, an innate immune cell subset critical for mounting an early 35 response to viral infection, are inhibited by self HLA class I, suggesting that upregulation of 36 HLA class I during DENV infection could dampen the NK cell response. Here we addressed 37 whether upregulation of HLA class I molecules occurs during in vivo DENV infection and, if so, 38

Objectives: Histoplasmosis and cryptococcosis are important public health problems in people living with HIV (PLHIV) in Central America. Conventional laboratory assays, based on microscopy and culture, are not optimal for the diagnosis of either disease.However, antigen (Ag) assays are rapid and highly accurate for the diagnosis of these infections. Methods: Laboratory surveillance of PLHIV was carried out in four hospitals in Panama, Honduras and Nicaragua, between 2015 and 2019. Detection of Histoplasma antigens in urine was performed by enzyme immunoassay (EIA), and Cryptococcus antigen detection in sera and cerebrospinal fluid specimens was performed by lateral flow assay (LFA). Results: A total of 4,453 PLHIV with clinical suspicion of histoplasmosis (n = 1,343) or cryptococcosis (n = 3,110; 2,721 sera and 389 CSF) were tested. Of 1,343 patients suspected of having histoplasmosis, 269 (20%) were Histoplasma Ag positive.Of 3,110 patients tested using the Cryptococcus Ag assay, 329 (11%) were positive.Honduras reported the highest positivity rates (32% for Histoplasma Ag, and 16% for Cryptococcus Ag); Panama reported the largest number of patients testing positive using the Histoplasma Ag assay (n = 201); and Nicaragua reported the largest number of patients testing positive using the Cryptococcus Ag assay (n = 170). Conclusion:Here, we show how the implementation of rapid diagnostics assays impacted case detection and was useful for the care of people with advanced HIV. Rapid and accurate diagnosis could reduce mortality associated with histoplasmosis and cryptococcosis in PLHIV.

Melioidosis is an infection caused by Burkholderia pseudomallei. Most cases occur in Southeast Asia and northern Australia; <100 cases have been reported in the Americas. We conducted a retrospective study and identified 12 melioidosis cases in Panama during 2007–2017, suggesting possible endemicity and increased need for surveillance.