Artemether–Lumefantrine Efficacy for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Choco, Colombia after 8 Years as First-Line Treatment

Olivera, Mario Javier; Guerra, Ángela Patricia; Cortés, Liliana Jazmín; Horth, Roberta; Padilla, Julio; Novoa, Jonathan; Adé, Maria Paz; Ljolje, Dragan; Lucchi, Naomi W.; Marquiño, Wilmer; Renteria, Martha; Yurgaky, Wilman; Oliveira, Alexandre Macedo de

doi:10.4269/ajtmh.19-0954

Cited by 18 publications

(22 citation statements)

References 25 publications

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“…This combination, used in the country since 2006, has shown efficacy rates > 95% in different endemic areas. [8][9][10][11] However, it is important to emphasize that circulating P. falciparum parasites have previously shown a propensity to develop drug resistance.…”

Section: Introductionmentioning

confidence: 99%

State of Artemisinin and Partner Drug Susceptibility in Plasmodium falciparum Clinical Isolates from Colombia

Montenegro

Salas

Neal

et al. 2021

The American Journal of Tropical Medicine and Hygiene

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Delayed parasite clearance time observed in Southeast Asia provided the first evidence of Plasmodium falciparum 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 pfmdr1 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 P. falciparum 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, pfmdr1 copy number, and pfmdr1 mutations at codons 86, 184, 1034, 1042, and 1246, associated with reduced susceptibility, and 50% inhibitory concentration (IC 50 ) 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 pfmdr1 haplotypes, NFSDD (79.3%) and NFSDY (20.7%), and 7.1% of isolates had > 1 pfmdr1 gene. In vitro IC 50 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 P. falciparum 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.

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Section: Introductionmentioning

confidence: 99%

State of Artemisinin and Partner Drug Susceptibility in Plasmodium falciparum Clinical Isolates from Colombia

Montenegro

Salas

Neal

et al. 2021

The American Journal of Tropical Medicine and Hygiene

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“…The results of this study show that the parasite density criterion is not really a relevant criterion for the definition of severe cases in Colombia, since the low levels of parasitemia observed in this large number of patients with severe malaria are similar to the levels found in patients with uncomplicated malaria [36,37]. Therefore, parasite density should certainly not be used to make a clinical decision about the severity of the disease.…”

Section: Plos Onementioning

confidence: 77%

Parasite density in severe malaria in Colombia

Padilla-Rodríguez¹,

Olivera²,

Guevara-García³

2020

PLoS ONE

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Background Colombia has officially adopted the parasite density levels of severe malaria established by the WHO (>50,000 parasites/μl). These values have been inferred from areas of high transmission in Africa and are not consistent with the dynamics of low and unstable transmission in Colombia. The objective of this study was therefore to determine the parasite density values observed in patients with severe malaria and their distribution in the different ecoepidemiological regions of Colombia. Methods A retrospective and descriptive study of confirmed cases of severe malaria was conducted in endemic areas of malaria in Colombia over the period 2014-2017. Data were collected from secondary sources of the Subnational Programs of Malaria Prevention and Control. Person, place, and time variables were selected. The official definition of severe malaria was adopted, and compliance with these criteria was determined. Univariate and bivariate analyses were conducted with absolute and relative frequency measures, and the relevant statistical tests were applied. Results The overall parasite density values in Colombia showed a geometric mean of 5,919 parasites/μl (95% CI: 5,608-6,248). By parasite species, the values were 6,151 (95% CI: 5,631-6,718) for Plasmodium falciparum and 5,815 (95% CI: 5,428-6,230) for Plasmodium vivax. The highest parasite density values were recorded in the Amazon ecoepidemiological region (8,177; 95% CI: 6,015-11,116), and the lowest values were recorded in the Andean region (5,026; 95% CI: 2,409-10,480). Conclusions In endemic areas of low and unstable malaria transmission in the Colombian territory, the parasite density levels observed in populations with severe malaria are lower than the officially established values. The parasite density criterion is not really a relevant criterion for the definition of severe cases in Colombia and it certainly not be used to make a clinical decision about the severity of the disease.

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“…The stratification and description of S4 showed that there are few municipalities with a predominance of P. falciparum transmission that are located in the Pacific region. This is an opportunity to prioritize these areas to implement strategies to start eliminating transmission of this parasite in Colombia [54]. On the other hand, municipalities with P. vivax transmission are distributed throughout ecoepidemiological regions, and the elimination of this parasite species represents a challenge to malaria elimination due to the presence of mature gametocytes at an early stage of infection, resulting in greater transmissibility and relapse by the activation of dormant hypnozoites [55][56][57][58].…”

Section: Discussionmentioning

confidence: 99%

“…falciparum transmission that are located in the Pacific region. This is an opportunity to prioritize these areas to implement strategies to start eliminating transmission of this parasite in Colombia [ 54 ]. On the other hand, municipalities with P .…”

Section: Discussionmentioning

confidence: 99%

Malaria risk stratification in Colombia 2010 to 2019

et al. 2021

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Background Heterogeneity and focalization are the most common epidemiological characteristics of endemic countries in the Americas, where malaria transmission is moderate and low. During malaria elimination, the first step is to perform a risk stratification exercise to prioritize interventions. This study aimed to identify malaria risk strata in the ecoepidemiological regions of Colombia. Methods This was a descriptive and retrospective study using cumulative malaria cases in 1,122 municipalities of Colombia from 2010 to 2019. To identify the strata, the criteria proposed by PAHO were adapted. To classify the receptive areas (strata 2, 3, and 4) and nonreceptive areas (stratum 1), 1,600 m above sea level, ecotypes, main malaria vector presence, Plasmodium species prevalence and occurrence of malaria cases were used. The area occupied by the receptive municipalities, the cumulative burden, and the at-risk population in the regions were calculated. Results Ninety-one percent of the Colombian territory is receptive to the transmission of malaria and includes 749 municipalities with 9,734,271 (9,514,243–9,954,299) million at-risk inhabitants. Stratum 4 accounted for 96.7% of the malaria burden, and cases were concentrated primarily in the Pacific and Uraba-Bajo Cauca-Sinu-San Jorge regions. Plasmodium vivax predominates in most of the receptive municipalities, except in the municipalities of the Pacific region, where P. falciparum predominates. Anopheles albimanus, An. nuneztovari s.l., and An. darlingi were the main vectors in receptive areas. Conclusions In Colombia, 91.2% of the territory is receptive to the transmission of malaria and is characterized by being both heterogeneous and focused. Stratum 4 contains the greatest burden of disease, with a relatively greater proportion of municipalities with a predominance of P. vivax. However, there is a low proportion of municipalities with P. falciparum mainly in the Pacific region. These findings suggest that the latter be prioritized within the malaria elimination plan in Colombia.

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Artemether–Lumefantrine Efficacy for the Treatment of Uncomplicated Plasmodium falciparum Malaria in Choco, Colombia after 8 Years as First-Line Treatment

Cited by 18 publications

References 25 publications

State of Artemisinin and Partner Drug Susceptibility in Plasmodium falciparum Clinical Isolates from Colombia

State of Artemisinin and Partner Drug Susceptibility in Plasmodium falciparum Clinical Isolates from Colombia

Parasite density in severe malaria in Colombia

Malaria risk stratification in Colombia 2010 to 2019

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