INAUGURAL ARTICLE by a Recently Elected Academy Member:Geographic patterns of Plasmodium falciparum drug resistance distinguished by differential responses to amodiaquine and chloroquine

Chloroquine (CQ) resistance (CQR) in Plasmodium falciparum originated from at least six foci in South America, Asia, and Oceania. Malaria parasites from these locations exhibit contrasting resistance phenotypes that are distinguished by point mutations and microsatellite polymorphisms in and near the CQR transporter gene, pfcrt, and the multidrug resistance transporter gene, pfmdr1. Amodiaquine (AQ), a 4-aminoquinoline related to CQ, is recommended and often used successfully against CQ-resistant P. falciparum in Africa, but it is largely ineffective across large regions of South America. The relationship of different pfcrt and pfmdr1 combinations to these drug-resistant phenotypes has been unclear. In two P. falciparum genetic crosses, particular pfcrt and pfmdr1 alleles from South America interact to yield greater levels of resistance to monodesethylamodiaquine (MDAQ; the active metabolite of AQ) than to CQ, whereas a pfcrt allele from Southeast Asia and Africa is linked to greater CQ than MDAQ resistance with all partner pfmdr1 alleles. These results, together with (i) available haplotype data from other parasites; (ii) evidence for an emerging focus of AQ resistance in Tanzania; and (iii) the persistence of 4-aminoquinoline-resistant parasites in South America, where CQ and AQ use is largely discontinued, suggest that different histories of drug use on the two continents have driven the selection of distinct suites of pfcrt and pfmdr1 mutations. Increasing use of AQ in Africa poses the threat of a selective sweep of highly AQ-resistant, CQ-resistant parasites with pfcrt and pfmdr1 mutations that are as advantaged and persistent as in South America.     

Admixture and recombination among Toxoplasma gondii lineages explain global genome diversity

Toxoplasma gondii is a highly successful protozoan parasite that infects all warm-blooded animals and causes severe disease in immunocompromised and immune-naïve humans. It has an unusual global population structure: In North America and Europe, isolated strains fall predominantly into four largely clonal lineages, but in South America there is great genetic diversity and the North American clonal lineages are rarely found. Genetic variation between Toxoplasma strains determines differences in virulence, modulation of host-signaling pathways, growth, dissemination, and disease severity in mice and likely in humans. Most studies on Toxoplasma genetic variation have focused on either a few loci in many strains or low-resolution genome analysis of three clonal lineages. We use whole-genome sequencing to identify a large number of SNPs between 10 Toxoplasma strains from Europe and North and South America. These were used to identify haplotype blocks (genomic regions) shared between strains and construct a Toxoplasma haplotype map. Additional SNP analysis of RNA-sequencing data of 26 Toxoplasma strains, representing global diversity, allowed us to construct a comprehensive genealogy for Toxoplasma gondii that incorporates sexual recombination. These data show that most current isolates are recent recombinants and cannot be easily grouped into a limited number of haplogroups. A complex picture emerges in which some genomic regions have not been recently exchanged between any strains, and others recently spread from one strain to many others.     

Survey of Wild Mammal Hosts of Cutaneous Leishmaniasis Parasites in Panamá and Costa Rica

The eco-epidemiology of American cutaneous leishmaniasis (ACL) is driven by animal reservoir species that are a source of infection for sand flies that serve as vectors infecting humans with Leishmania spp parasites. The emergence and re-emergence of this disease across Latin America calls for further studies to identify reservoir species associated with enzootic transmission. Here, we present results from a survey of 52 individuals from 13 wild mammal species at endemic sites in Costa Rica and Panama where ACL mammal hosts have not been previously studied. For Leishmania spp. diagnostics we employed a novel PCR technique using blood samples collected on filter paper. We only found Leishmania spp parasites in one host, the two-toed sloth, Choloepus hoffmanni. Our findings add further support to the role of two-toed sloths as an important ACL reservoir in Central America.     

New and Emerging Viruses of Blueberry and Cranberry

Blueberry and cranberry are fruit crops native to North America and they are well known for containing bioactive compounds that can benefit human health. Cultivation is expanding within North America and other parts of the world raising concern regarding distribution of existing viruses as well as the appearance of new viruses. Many of the known viruses of these crops are latent or asymptomatic in at least some cultivars. Diagnosis and detection procedures are often non-existent or unreliable. Whereas new viruses can move into cultivated fields from the wild, there is also the threat that devastating viruses can move into native stands of Vaccinium spp. or other native plants from cultivated fields. The aim of this paper is to highlight the importance of blueberry and cranberry viruses, focusing not only on those that are new but also those that are emerging as serious threats for production in North America and around the world.     

The Contribution of Bats to Leptospirosis Transmission in S?o Paulo City,Brazil

The biodiversity of potential leptospiral reservoir hosts is lower in urban than in rural environments. Previous data indicate the potential for bats to act as carriers of Leptospira in regions such as the Amazon of South America and in Australia. Yet, little is known about the contribution of bats to leptospirosis in urban environments in South America. This study aimed to test the hypothesis that bats infected with Leptospira are sources of leptospirosis transmission to humans in São Paulo City, Brazil. Six of 343 bats caught in different districts within the city of Sao Paulo (182 insectivorous, 161 frugivorous or nectarivorous) were polymerase chain reaction (PCR) positive for pathogenic Leptospira; no seropositive bats were found. That few renal carriers of Leptospira were found in the city of Sao Paulo suggests that bats are not important in the transmission of leptospirosis to humans in this, and possibly other urban settings.     

First study of Seoul virus (SEOV) in urban rodents from newly urbanized areas of Gran La Plata,Argentina

Alterations of ecosystems have deep effects on the distribution of parasites. Big cities of Argentina present structural features that favor the presence of synanthropic species, acting as source of zoonotic diseases, for example in urban rodents: the Norway rat (Rattus norvegicus) and the black rat (R. rattus). One of the important zoonotic pathogens related are the RNA virus Hantavirus, with high prevalence rates in South America. The aim of this study was to explore and identify the presence of Hantavirus in urban rodents from Gran La Plata, Argentina. The presence of anti-hantavirus IgG antibodies was determined by the Enzyme-Linked Immunosorbent Assay. Six samples turned out positive for Seoul virus (SEOV, p = 14.3%). These are the first records of SEOV in urban rodents in Gran La Plata. It represents the first report in R. rattus in Argentina, and in America. This situation underscores the inequality and historical forgetfulness of a portion of society, calling for urgent action to be taken in this regard.     

New description of Toxoplasma gondii genotypes from French Polynesia

We report here the first isolation and genotyping of two human Toxoplasma gondii strains from French Polynesia. The parasites had new and atypical genotypes, and were responsible for asymptomatic congenital toxoplasmosis. Both genotypes were divergent from the common strains isolated in Europe, North America, South America, Africa and China.     

Role of gene polymorphisms in gastric cancer and its precursor lesions:Current knowledge and perspectives in Latin American countries

Latin America shows one of the highest incidence rates of gastric cancer in the world,with variations in mortality rates among nations or even within countries belonging to this region.Gastric cancer is the result of a multifactorial complex process,for which a multistep model of carcinogenesis is currently accepted.Additionally to the infection with Helicobacter pylori,that plays a major role,environmental factors as well as genetic susceptibility factors are significant players at different stages in the gastric cancer process.The differences in population origin,demographic structure,socio-economic development,and the impact of globalization lifestyles experienced in Latin America in the last decades,all together offer opportunities for studying in this context the influence of genetic polymorphisms in the susceptibility to gastric cancer.The aim of this article is to discuss current trends on gastric cancer in Latin American countries and to review the available published information about studies of association of gene polymorphisms involved in gastric cancer susceptibility from this region of the world.A total of 40 genes or genomic regions and69 genetic variants,58%representing markers involved in inflammatory response,have been used in a number of studies in which predominates a low number of individuals(cases and controls)included.Polymorphisms of IL-1B(-511 C/T,14 studies;-31 T/C,10 studies)and IL-1RN(variable number of tandem repeats,17 studies)are the most represented ones in the reviewed studies.Other genetic variants recently evaluated in large metaanalyses and associated with gastric cancer risk were also analyzed in a few studies[e.g.,prostate stem cell antigen(PSCA),CDH1,Survivin].Further and better analysis centered in gene polymorphisms linked to other covariates,epidemiological studies and the information provided by meta-analyses and genome-wide association studies should help to improve our understanding of gastric cancer etiology in order to develop appropriate health programs in Latin America.     

Nuclear ribosomal DNA evidence for a western North American origin of Hawaiian and South American species of Sanicula (Apiaceae)

Results from phylogenetic analysis of nuclear rDNA internal transcribed spacer (ITS) sequences from a worldwide sample of Sanicula indicate that Hawaiian sanicles (Sanicula sect. Sandwicenses) constitute a monophyletic group that descended from a western North American ancestor in Sanicula sect. Sanicoria, a paraphyletic assemblage of mostly Californian species. A monophyletic group comprising representatives of all 15 species of S. sect. Sanicoria and the three sampled species of S. sect. Sandwicenses was resolved in all maximally parsimonious trees, rooted with sequences from species of Astrantia and Eryngium. All sequences sampled from eastern North American, European, and Asian species of Sanicula fell outside the ITS clade comprising S. sect. Sanicoria and S. sect. Sandwicenses. A lineage comprising the Hawaiian taxa and three species endemic to coastal or near-coastal habitats in western North America (Sanicula arctopoides, Sanicula arguta, and Sanicula laciniata) is diagnosed by nucleotide substitutions and a 24-bp deletion in ITS2. The hooked fruits in Sanicula lead us to conclude that the ancestor of Hawaiian sanicles arrived from North America by external bird dispersal; similar transport has been hypothesized for the North American tarweed ancestor of the Hawaiian silversword alliance (Asteraceae). Two additional long-distance dispersal events involving members of S. sect. Sanicoria can be concluded from the ITS phylogeny: dispersal of Sanicula crassicaulis and Sanicula graveolens from western North America to southern South America.     

A hummingbird-pollinated species of boraginaceae in the Arizona flora

Marcomeria viridiflora (Boraginaceae) is pollinated by broad-tailed and rufous hummingbirds in the White Mountains of Arizona. This is the first hummingbird-pollinated member of the family Boraginaceae to be recorded in western North America. It provides one more example of a predominantly beepollinated plant group that has given rise to one or a few exceptional species of hummingbird flowers in western North America.     

Distribution of filamentous fungi causing invasive fungal disease at the Haematological Unit,Hospital de Clínicas de Porto Alegre,Brazil

Very limited data are available in the literature to elucidate the aetiology of invasive mould infections in Latin America. Here we report that Aspergillus species caused only half of such cases in a cohort study conducted over 21 months in a university hospital in Porto Alegre, Southern Brazil. Fusarium spp. were the second most prevalent moulds (20.7%), followed by Zygomycetes (13.8%). The importance of obtaining local epidemiological data for adequately guiding empirical antifungal therapy is reinforced.     

Regional Variation in the Correlation of Antibody and T-Cell Responses to Trypanosoma cruzi

Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, is a major cause of morbidity and mortality in Central and South America. Geographic variations in the sensitivity of serologic diagnostic assays to T. cruzi may reflect differences in T. cruzi exposure. We measured parasite-specific T-cell responses among seropositive individuals in two populations from South America with widely varying antibody titers against T. cruzi. Antibody titers among seropositive individuals were significantly lower in Arequipa, Peru compared with Santa Cruz, Bolivia. Similarly, the proportion of seropositive individuals with positive T-cell responses was lower in Peru than Bolivia, resulting in overall lower frequencies of interferon-γ (IFNγ)-secreting cells from Peruvian samples. However, the magnitude of the IFNγ response was similar among the IFNγ responders in both locations. These data indicate that immunological discrepancies based on geographic region are reflected in T-cell responses as well as antibody responses.     

Systemic therapy of New World cutaneous leishmaniasis: A case report and review article

Cutaneous leishmaniasis is a disease endemic to Central and South America, Mexico and the Caribbean, and affects millions of people. As travel to these regions becomes more common, cutaneous leishmaniasis is becoming a disease of increasing importance in the developed world. However, disease recognition and access to appropriate therapy for cutaneous leishmaniasis remains a challenge in North America. The present article reports a case of cutaneous leishmaniasis in a Canadian man following a trip to Costa Rica. Species-specific diagnosis was confirmed by polymerase chain reaction analysis of a skin biopsy, which was positive for Leishmania panamensis. After failing a course of itraconazole, the patient was successfully treated with sodium stibogluconate, despite significant barriers to administering this therapy, and the paucity of data regarding its efficacy and tolerability. The pathophysiology, diagnosis and systemic treatment of cutaneous leishmaniasis, as well as its emerging presence in the developed world, are reviewed.     

Epidemiology of Sexual Health in the Virtual Environment: A Multinational Online Survey of Spanish- and Portuguese-Speaking Men who use an Internet Sexual Networking Site

There is limited data on the sexual health of users of sexual networking websites for men who have sex with men (MSM) in Latin America. Members of a MSM-targeted social/sexual networking website in Latin America, Spain, and Portugal participated in an online sexual health survey. Among 36,063 respondents, nearly 90 % reported having anal or vaginal intercourse in the past 3 months. Among sexually active men, 53.2 % used condoms inconsistently. In the past year, 54 % of respondents reported undergoing sexually transmitted infections (STI) testing and 67 % reported testing yearly or more often for HIV. Self-reported HIV prevalence was 9.1 %. Differences were seen by geographic region. Unprotected intercourse with partners of different or unknown HIV status was associated with recent STI diagnosis (OR = 1.83, t = 13.15, d.f. = 21, p < .001) and HIV diagnosis (OR = 2.20, t = 14.00, d.f. = 21, p < .001). Online surveys are a promising tool for HIV/STI surveillance and prevention internationally to reach an important subset of MSM.     

Further Characterization of Rio Grande Virus and Potential for Cross Reactivity with Rift Valley Fever Virus Assays

Phleboviruses (genus Phlebovirus, family Phenuiviridae) are emerging pathogens of humans and animals. Sand-fly-transmitted phleboviruses are found in Europe, Africa, the Middle East, and the Americas, and are responsible for febrile illness and nervous system infections in humans. Rio Grande virus (RGV) is the only reported phlebovirus in the United States. Isolated in Texas from southern plains woodrats, RGV is not known to be pathogenic to humans or domestic animals, but serologic evidence suggests that sheep (Ovis aries) and horses (Equus caballus) in this region have been infected. Rift Valley fever virus (RVFV), a phlebovirus of Africa, is an important pathogen of wild and domestic ruminants, and can also infect humans with the potential to cause severe disease. The introduction of RVFV into North America could greatly impact U.S. livestock and human health, and the development of vaccines and countermeasures is a focus of both the CDC and USDA. We investigated the potential for serologic reagents used in RVFV diagnostic assays to also detect cells infected with RGV. Western blots and immunocytochemistry assays were used to compare the antibody detection of RGV, RVFV, and two other New World phlebovirus, Punta Toro virus (South and Central America) and Anhanga virus (Brazil). Antigenic cross-reactions were found using published RVFV diagnostic reagents. These findings will help to inform test interpretation to avoid false positive RVFV diagnoses that could lead to public health concerns and economically costly agriculture regulatory responses, including quarantine and trade restrictions.     

Extended spectrum β-lactamase producers among nosocomial Enterobacteriaceae in Latin America

To review the epidemiology of nosocomial extended spectrum β-lactamase-producing Enterobacteriaceae in Latin America, a systematic search of the biomedical literature (PubMed) was performed for articles published since 2005. Rates of nosocomial infections caused by extended spectrum β-lactamase-producing Enterobacteriaceae in Latin America have increased since 2005. Up to 32% of Escherichia coli and up to 58% of Klebsiella pneumoniae isolates are extended spectrum β-lactamase-positive, rates that are higher than in other world regions. From a region-wide perspective, 11–25% of E. coli isolates and 45–53% of K. pneumoniae isolates were nonsusceptible to third-generation cephalosporins. At the country level, there was a wide range in Enterobacteriaceae resistance rates to third-generation cephalosporins, with especially high rates of resistance to E. coli in Guatemala, Honduras, and Mexico, and high resistance rates to Klebsiella spp. in Argentina, Brazil, Chile, Guatemala, Honduras, and Paraguay. Susceptibility of extended spectrum β-lactamase-producing Enterobacteriaceae to cefepime, fluoroquinolones, ampicillin/sulbactam, aminoglycosides, and piperacillin/tazobactam has also been compromised, leaving the carbapenems, tigecycline, and colistin as the only antibiotics with >90% susceptibility rates. There is a steady increase in the prevalence and types of extended spectrum β-lactamases produced by Enterobacteriaceae isolates in Latin American hospitals (particularly CTX-Ms), suggesting endemic conditions overlaid by clonal outbreaks. Appropriate treatment decisions and infection control strategies informed by surveillance of regional and local susceptibilities and mechanisms of resistance are required to mitigate this major public health concern.     

Guatemalan forest synthesis after Pleistocene aridity

Sediments from two lakes in the Peten Department, Guatemala, provide palynological evidence from Central America of late Pleistocene aridity and subsequent synthesis of mesic forests. Late Glacial vegetation consisted of marsh, savanna, and juniper scrub. An early Holocene temperate forest preceded a mesic tropical forest with Brosimum (ramon). Thus “primeval” rain forests of Guatemala are no older than 10,000 to 11,000 years and are considerably younger in the Peten due to Mayan disturbances. Among dated Neotropical sites, the Peten has the most mesic vegetation yet shown to have supplanted xeric vegetation present during the Pleistocene. The arid late Glacial-humid early Holocene transition appears to have been pantropical in the lowlands. The Peten was not a Pleistocene refugium for mesophytic taxa, as has been suggested. Thus genesis of extant rain forests in northern Central America and southern Mexico remains unexplained.     

Evolution of mitochondrial DNA in Drosophila subobscura

The colonization of the New World by the Palearctic species Drosophila subobscura was first detected in 1978 in South America and around 1982 in western North America. The ensuing dramatic expansion of the species, in territory as well as numbers, provides an opportunity for studying evolution in a scale rarely possible. We have used 10 restriction endonucleases to analyze the mitochondrial DNA (mtDNA) of individuals from 23 widely dispersed localities. Only two mtDNA composite morphs have been detected in the Americas. None of the two morphs has been found in Africa, and only one in the Atlantic islands; but both are widespread in Europe, which provides no clue of the precise geographic origin of the colonizers. The amount of nucleotide-substitution polymorphism detected in D. subobscura is typical for animals, but it is greater in the Old than in the New World, presumably due to the recent colonization by a limited number of colonizers. Assuming standard evolutionary rates of mtDNA base substitution, the mtDNA morphs found in D. subobscura can be traced to a single one that existed no less than one million years ago. We argue against the inference that the D. subobscura flies now living descend from only one or a few females that lived at that time. This type of inference, which we call the “Mother Eve hypothesis,” has been made to conclude that the human population went through a severe constriction about 200,000 years ago, so that all living humans descend from only one or a few women who lived at that time. The Mother Eve hypothesis is fallacious.     

Relevance of Eosinophilia and Hyper-IgE in Immigrant Children

Immigrants from undeveloped countries are a growing problem in Europe. Spain has become a frequent destination for immigrants (20% of whom are children) because of its geographic location and its historic and cultural links with Africa and Latin America. Eosinophilia is frequent in adult immigrants, travelers and expatriates coming from tropical areas. However, there are few studies that focus on the incidence and causes of tropical eosinophilia and hyper-IgE in immigrant children.We evaluated, prospectively, the prevalence and causes of eosinophilia and hyper-immunoglobulin E (IgE) in 362 immigrant children coming from Sub-Saharan Africa, Northern Africa and Latin America to Salamanca, Spain, between January 2007 and December 2011.Absolute eosinophilia and hyper-IgE were present in 22.9% and 56.8% of the analyzed children, respectively. The most frequent causes of absolute eosinophilia were filariasis (52.6%), strongyloidiasis (46.8%) and schistosomiasis (28.9%). Filariasis (41.9%), strongyloidiasis (29.6%) and schistosomiasis (22.2%) were the most frequent causes of increased levels of IgE. The area under the ROC curve showed similar values between eosinophil count and IgE levels in the diagnosis of helminthiasis (69% [95% confidence interval (CI) 63%–74%] vs 67% [95% CI 60%–72%], P = 0.24). Eosinophilia and hyper-IgE have a high value as biomarkers of helminthiasis in children coming from tropical and subtropical areas.     

Mobile genetic elements associated with carbapenemase genes in South American Enterobacterales

IntroductionCarbapenem resistance in members of order Enterobacterales is a growing public health problem causing high mortality in developing and industrialized countries. Its emergence and rapid propagation worldwide was due to both intercontinental spread of pandemic strains and horizontal dissemination via mobile genetic elements (MGE) such as plasmids and transposons.ObjectiveTo describe MGE carrying carbapenem resistance genes in Enterobacterales which have been reported in South America.Search strategy and selection criteriaA search of the literature in English or Spanish published until 2019 in PubMed, Google Scholar, LILACS and SciELO databases was performed for studies of MGE in Enterobacterales reported in South American countries.ResultsSeven South American countries reported MGE related to carbapenemases. Carbapenemase-producing Klebsiella pneumoniae belonging to clonal complex 258 were the most prevalent pathogens reported; others carbapenemase-producing Enterobacterales such as Escherichia coli, Serratia marcescens, and Providencia rettgeri also have been reported. The MGE implicated in the spread of the most prevalent carbapenemase genes are Tn4401 and non-Tn4401 elements for bla_KPC and ISAba125 for bla_NDM, located in different plasmid incompatibility groups, i.e. L/M, A/C, FII and bacterial clones.ConclusionThis review indicates that, like in other parts of the world, the most commonly reported carbapenemases in Enterobacterales from South America are being disseminated through clones, plasmids, and transposons which have been previously reported in other parts of the world.