Determinación de genotipos circulantes de loci asociados a la resistencia a drogas antimaláricas en Plasmodium falciparum en la población de Guapi, Departamento del Cauca, Colombia

En Colombia la malaria representa un problema prioritario de salud pública. Se recomienda vigilar regularmente en cada zona endémica la falla terapéutica y la resistencia a los medicamentos antimaláricos con el fin de diseñar esquemas de tratamiento adecuados y detectar tempranamente cambios en el grado de susceptibilidad. Factores como el historial de regímenes de manejo de la malaria no complicada para infecciones por P falciparum en el país, condiciones ecológicas que afectan la transmisión, aparición de nuevas mutaciones que otorgan resistencia y la migración de poblaciones a través de barreras naturales características de la geografía del país pueden afectar la distribución y frecuencia de genotipos resistentes a las drogas antimaláricas. El estudio de la genética de poblaciones de Plasmodium brinda información valiosa acerca de características biológicas de los parásitos, la dinámica de la transmisión de la malaria y la resistencia a drogas antimaláricas, entre otras fuerzas evolutivas que condicionan el estado natural de sus poblaciones. Perteneciente a la región Pacífica, Guapi en el departamento del Cauca, Colombia, es una zona de transmisión de malaria endémica, tiene una intensidad de transmisión baja y el principal agente causante de la enfermedad es P. falciparum. Este estudio surge con el fin de investigar los genotipos asociados a resistencia a antimaláricos en poblaciones naturales de P. falciparum. Se analizaron muestras provenientes de pacientes positivos para el diagnóstico de malaria por P falciparum del municipio de Guapi. Se obtuvieron datos de las frecuencias de los alelos mutantes circulantes asociados con la resistencia a cloroquina, sulfadoxina, pirimetamina y artemisinina y se obtuvieron datos indicadores de diversidad genética en loci microsatelitales no sometidos a presión selectiva. Se reporta la mutación S436F no antes reportada en el departamento del Cauca y recientemente reportada en la zona oriental del país, los marcadores microsatelitales neutros sugieren un origen local de ésta mutación nueva. Los resultados obtenidos en este trabajo sugieren un perfil de resistencia baja a Sulfadoxina-Pirimetamina y derivados de artemisinina en el municipio de Guapi y poblaciones cercanas. Este estudio aporta datos importantes en la detección de mutaciones asociadas a resistencia, características de la genética de poblaciones de Plasmodium falciparum en la frontera de los departamentos de Nariño y Cauca y ayuda a esclarecer el camino en el diseño de esquemas de tratamiento adecuados y programas de vigilancia epidemiológica.Abstract: Malaria represents an important public health issue in Colombia. It is recommended to monitor regularly the therapeutic failure and antimalarial drugs resistance in endemic areas in order to design appropriate treatment schemes and detect changes in susceptibility. The distribution and frequency of genotypes resistant to antimalarial drugs can be affected by factors such as the history of management regimens for P. falciparum infections, ecological conditions that affect transmission, emergence of new mutations that provide resistance and the migration of populations through natural barriers characteristic of the geography of the country. The study of Plasmodium population genetics provides valuable information about the parasite biology, malaria transmission dynamics and antimalarial drugs resistance, among other evolutionary forces that condition the natural state of populations. Guapi in the department of Cauca, Colombia, is an area of endemic malaria transmission. Guapi has a low transmission intensity and the main causative agent of the disease is P. falciparum. This study aim is to investigate the genotypes associated with antimalarial resistance in natural populations of P. falciparum. Samples from patients positive for the diagnosis of malaria due to P falciparum in the municipality of Guapi were analyzed. Data of frequencies of the circulating mutant alleles associated with resistance to chloroquine, sulfadoxine, pyrimethamine and artemisinin were obtained. Genetic diversity index were obtained from microsatellite loci not subjected to selective pressure. We report the S436F mutation not previously reported in the department of Cauca and recently reported in the eastern part of the country, the neutral microsatellite markers suggest a local origin of this new mutation. The results obtained in this work suggest a low resistance profile to sulfadoxinepyrimethamine and artemisinin derivatives in the municipality of Guapi and nearby populations. This study provides important data in the detection of mutations associated with resistance, characteristics of the genetics of populations of Plasmodium falciparum in the border of the departments of Nariño and Cauca and helps in designing appropriate treatment schemes and programs for epidemiological surveillance.Maestrí

Spatio-temporal dynamics of Plasmodium falciparum transmission within a spatial unit on the Colombian Pacific Coast

Funder: Newton-Caldas Fund Institutional Links, British Council, award G1854Funder: Newton-Caldas Fund Institutional Links, British Council, award G1854; Faculty of Medicine, Universidad Nacional de Colombia, awards HERMES 35988, 32309Abstract: As malaria control programmes concentrate their efforts towards malaria elimination a better understanding of malaria transmission patterns at fine spatial resolution units becomes necessary. Defining spatial units that consider transmission heterogeneity, human movement and migration will help to set up achievable malaria elimination milestones and guide the creation of efficient operational administrative control units. Using a combination of genetic and epidemiological data we defined a malaria transmission unit as the area contributing 95% of malaria cases diagnosed at the catchment facility located in the town of Guapi in the South Pacific Coast of Colombia. We provide data showing that P. falciparum malaria transmission is heterogeneous in time and space and analysed, using topological data analysis, the spatial connectivity, at the micro epidemiological level, between parasite populations circulating within the unit. To illustrate the necessity to evaluate the efficacy of malaria control measures within the transmission unit in order to increase the efficiency of the malaria control effort, we provide information on the size of the asymptomatic reservoir, the nature of parasite genotypes associated with drug resistance as well as the frequency of the Pfhrp2/3 deletion associated with false negatives when using Rapid Diagnostic Tests

Spatio-temporal dynamics of Plasmodium falciparum transmission within a spatial unit on the Colombian Pacific Coast.

As malaria control programmes concentrate their efforts towards malaria elimination a better understanding of malaria transmission patterns at fine spatial resolution units becomes necessary. Defining spatial units that consider transmission heterogeneity, human movement and migration will help to set up achievable malaria elimination milestones and guide the creation of efficient operational administrative control units. Using a combination of genetic and epidemiological data we defined a malaria transmission unit as the area contributing 95% of malaria cases diagnosed at the catchment facility located in the town of Guapi in the South Pacific Coast of Colombia. We provide data showing that P. falciparum malaria transmission is heterogeneous in time and space and analysed, using topological data analysis, the spatial connectivity, at the micro epidemiological level, between parasite populations circulating within the unit. To illustrate the necessity to evaluate the efficacy of malaria control measures within the transmission unit in order to increase the efficiency of the malaria control effort, we provide information on the size of the asymptomatic reservoir, the nature of parasite genotypes associated with drug resistance as well as the frequency of the Pfhrp2/3 deletion associated with false negatives when using Rapid Diagnostic Tests

Spatio-temporal dynamics of Plasmodium falciparum transmission within a spatial unit on the Colombian Pacific Coast

As malaria control programmes concentrate their efforts towards malaria elimination a better understanding of malaria transmission patterns at fine spatial resolution units becomes necessary. Defining spatial units that consider transmission heterogeneity, human movement and migration will help to set up achievable malaria elimination milestones and guide the creation of efficient operational administrative control units. Using a combination of genetic and epidemiological data we defined a malaria transmission unit as the area contributing 95% of malaria cases diagnosed at the catchment facility located in the town of Guapi in the South Pacific Coast of Colombia. We provide data showing that P. falciparum malaria transmission is heterogeneous in time and space and analysed, using topological data analysis, the spatial connectivity, at the micro epidemiological level, between parasite populations circulating within the unit. To illustrate the necessity to evaluate the efficacy of malaria control measures within the transmission unit in order to increase the efficiency of the malaria control effort, we provide information on the size of the asymptomatic reservoir, the nature of parasite genotypes associated with drug resistance as well as the frequency of the Pfhrp2/3 deletion associated with false negatives when using Rapid Diagnostic Tests. © 2020, The Author(s)