Self-medication with antimalarial drugs is a major factor in the development of drug resistance, exerting subtherapeutic drug pressure on circulating parasite populations. Data on self-medication ...with antimalarials from the Southern Pacific coast region of Colombia, where 4-aminoquinolines resistance and political instability prevail, are vital to elimination strategies. We present results of an exploratory study of 254 individuals having malaria symptoms who sought malaria diagnosis in two hospitals in Tumaco, Department of Nariño, Colombia. Thirty-two percent (82/254) of participants had positive Saker-Solomons urine tests, indicating self-medication with chloroquine (CQ) before consultation for diagnosis. Notably, among 30 pregnant women participating in the study, 43% were Saker--Solomons positive. Molecular analysis of the K76T position encoded by the
gene revealed the mutant allele in all four samples that were both positive for
and positive for the Saker-Solomons test, suggesting persistent CQ pressure. The high frequency of self-medication, particularly among pregnant women merits attention by public health authorities and comprehensive investigation.
Traditionally, patient travel history has been used to distinguish imported from autochthonous malaria cases, but the dormant liver stages of Plasmodium vivax confound this approach. Molecular tools ...offer an alternative method to identify, and map imported cases. Using machine learning approaches incorporating hierarchical fixation index and decision tree analyses applied to 799 P. vivax genomes from 21 countries, we identified 33-SNP, 50-SNP and 55-SNP barcodes (GEO33, GEO50 and GEO55), with high capacity to predict the infection's country of origin. The Matthews correlation coefficient (MCC) for an existing, commonly applied 38-SNP barcode (BR38) exceeded 0.80 in 62% countries. The GEO panels outperformed BR38, with median MCCs > 0.80 in 90% countries at GEO33, and 95% at GEO50 and GEO55. An online, open-access, likelihood-based classifier framework was established to support data analysis (vivaxGEN-geo). The SNP selection and classifier methods can be readily amended for other use cases to support malaria control programs.
Abstract The genomic characteristics of Peruvian patients with gastric adenocarcinoma from diverse socioeconomic backgrounds were examined in consideration of the possibility that patients from ...different socioeconomic backgrounds may be exposed to different risk factors. We conducted a prospective pilot study in two Peruvian cities (Lima and Ica). This study enrolled 15 patients from low socioeconomic status (LSES) and 15 patients from medium/high socioeconomic status (MHSES). The genomic profiling of gastric adenocarcinoma samples was done through the FoundationOne CDx platform. We compared the genomic characteristics and the need for targeted therapy and immunotherapy between LSES and MHSES. The genes with higher rates of alterations were TP53 (73.3% vs. 50.0%, P = 0.2635); CDH1 (26.7% vs. 28.6%, P = 1); CDKN2A (20.0% vs. 28.6%, P = 1); KRAS (33.3% vs. 7.1%, P = 0.1686); ARID1A (20.0% vs. 14.3%, P = 1); MLL2 (13.3% vs. 21.4%, P = 1) and SOX9 (33.3% vs. 0.0%, P = 0.0421) in LSES versus HMSES, respectively. There was no significant difference in tumor mutational burden ( P = 0.377) or microsatellite status ( P = 1). The LSES group had a higher need for targeted therapy or immunotherapy according to gene involvement and alterations. A significant genomic difference exists among patients with gastric adenocarcinoma of different socioeconomic status, which may result in a different need for targeted therapy and immunotherapy.
Delayed parasite clearance time observed in Southeast Asia provided the first evidence of
resistance to artemisinins. The ex vivo ring-stage survival assay (RSA) mimics parasite exposure to ...pharmacologically relevant artemisinin concentrations. Mutations in the C-terminal propeller domain of the putative kelch protein Pf3D7_1343700 (K13) are associated with artemisinin resistance. Variations in the
gene are associated with reduced susceptibility to the artemisinin partner drugs mefloquine (MQ) and lumefantrine (LF). To clarify the unknown landscape of artemisinin resistance in Colombia, 71 patients with uncomplicated
malaria were enrolled in a non-randomized observational study in three endemic localities in 2014-2015. Each patient's parasite isolate was assessed for ex vivo RSA, K13-propeller mutations,
copy number, and
mutations at codons 86, 184, 1034, 1042, and 1246, associated with reduced susceptibility, and 50% inhibitory concentration (IC
) for other antimalarial drugs. Ex vivo RSAs were successful in 56% (40/71) of samples, and nine isolates showed survival rates > 1%. All isolates had wild-type K13-propeller sequences. All isolates harbored either of two
haplotypes, NFSDD (79.3%) and NFSDY (20.7%), and 7.1% of isolates had > 1
gene. In vitro IC
assays showed that variable proportions of isolates had decreased susceptibility to chloroquine (52.4%, > 100 nM), amodiaquine (31.2%, > 30 nM), MQ (34.3%, > 30 nM), and LF (3.2%, > 10 nM). In this study, we report ex vivo RSA and K13 data on
isolates from Colombia. The identification of isolates with increased ex vivo RSA rates in the absence of K13-propeller mutations and no positivity at day three requires further investigation.
Colombia aims to eliminate malaria by 2030 but remains one of the highest burden countries in the Americas. Plasmodium vivax contributes half of all malaria cases, with its control challenged by ...relapsing parasitaemia, drug resistance and cross-border spread. Using 64 Colombian P. vivax genomes collected between 2013 and 2017, we explored diversity and selection in two major foci of transmission: Chocó and Córdoba. Open-access data from other countries were used for comparative assessment of drug resistance candidates and to assess cross-border spread. Across Colombia, polyclonal infections were infrequent (12%), and infection connectivity was relatively high (median IBD = 5%), consistent with low endemicity. Chocó exhibited a higher frequency of polyclonal infections (23%) than Córdoba (7%), although the difference was not significant (P = 0.300). Most Colombian infections carried double pvdhfr (95%) and single pvdhps (71%) mutants, but other drug resistance mutations were less prevalent (< 10%). There was no evidence of selection at the pvaat1 gene, whose P. falciparum orthologue has recently been implicated in chloroquine resistance. Global population comparisons identified other putative adaptations. Within the Americas, low-level connectivity was observed between Colombia and Peru, highlighting potential for cross-border spread. Our findings demonstrate the potential of molecular data to inform on infection spread and adaptation.
The neotropical climate of Central America provides ideal conditions for ticks, which may transmit several human pathogens, including spotted-fever group Rickettsia. Dogs may act as sentinels or ...reservoirs for human tick-borne diseases due to shared tick species. Here, ticks were collected from 680 client-owned dogs in Nicaragua and Costa Rica, and a total of 316 tick pools were investigated for Rickettsia infection by quantitative real-time PCR (qPCR) targeting the gltA gene. Subsequently, up to six further genomic targets (16S rDNA, gltA, sca4, ompA, ompB and the 23S-5S intergenic spacer) were investigated for Rickettsia species determination. The predominant tick species was Rhipicephalus sanguineus sensu lato (s.l.) (19.9% of dogs infested in Costa Rica, 48.0% in Nicaragua), followed by Ixodes boliviensis (3.1% in Costa Rica / none in Nicaragua) and Amblyomma ovale (4.8% in Costa Rica, 0.9% in Nicaragua). In total, 22 of 316 tick pools containing 60 of 1023 individual ticks were Rickettsia-positive as determined by qPCR, resulting in a minimum infection rate (MIR) of 2.2%. In detail, MIR in Rh. sanguineus s.l. was 0.7% (7/281 pools), in I. boliviensis 33.3% (12/13 pools) and in A. ovale 9.7% (3/22 pools). For 11 of 12 positive I. boliviensis pools and one of six positive Rh. sanguineus s.l. pools, the species could be determined as R. monacensis. R. amblyommatis was identified in one Rh. sanguineus s.l. pool from Costa Rica and one A. ovale pool from Nicaragua. Nine of 12 R. monacensis-positive tick pools were collected in San Rafael de Heredia, Costa Rica, indicating a high local occurrence in this area. This study supports recent evidence that R. monacensis is present on the American continent. Its high local occurrence among dog-associated I. boliviensis, which may also parasitize humans, in Costa Rica gives cause for concern, as R. monacensis is also pathogenic to humans.
We evaluated the clinical and epidemiologic characteristics of Peruvian children presenting with pulmonary tuberculosis (PTB) to determine whether features predictive of confirmed PTB could be ...identified.
This was a cross-sectional study of 135 children (mean age: 6.8 years) presenting to the Hospital del Niño in Lima, Peru, with presumptive diagnosis of PTB. Clinical, epidemiologic, and laboratory findings were compared between 3 groups of pediatric patients with a presumptive diagnosis of PTB: those with positive Mycobacterium tuberculosis (MTB) cultures, those likely to have PTB based on clinical criteria but with negative cultures, and those who did not meet clinical diagnostic criteria or have positive cultures.
A total of 50 (37%) patients were diagnosed with definitive PTB based on positive sputum culture. Another 55 (47%) patients were classified as having probable PTB based on meeting at least 2 of the following criteria: cough lasting for at least 2 weeks, typical chest radiograph changes, purified protein derivative (PPD) >/=10 mm, or history of tuberculosis family contact. Patients with definitive or probable PTB were significantly older than patients without clinical PTB, and those with symptomatic disease were significantly older than those with asymptomatic disease. Patients with PTB diagnosed by culture were significantly more likely than those diagnosed using clinical criteria to have cough lasting >/=2 weeks, fever, and a PPD >/=10 mm.
The typical presentation of PTB in Peruvian children includes symptoms of active pulmonary disease similar to those seen in adults. This presentation differs significantly from that reported in developed countries, where many children have minimal or no symptoms at the time of presentation. The diagnostic criteria for pediatric PTB must be modified in hyperendemic developing country environments where features may differ from those described in the United States. The triad of cough lasting >/=2 weeks, fever, and a PPD >/=10 mm was highly predictive for culture-positive PTB among children in this low-income Peruvian population.
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