In vitro susceptibility of Colombian Plasmodium falciparum isolates to different antimalarial drugs
Keywords:
malaria/therapy, Plasmodium falciparum, antimalarials, drug resistance, Colombia
Abstract
Introduction. The in vitro assays for susceptibility of Plasmodium falciparum to antimalarial drugs are important tools for monitoring drug resistance, however few such studies have been undertaken in Colombia.Objective. P. falciparum isolates were obtained from several municipalities in western Colombia (Urabá, Bajo Cauca, Pacific Coast) and characterized for their in vivo susceptibility to chloroquine (CQ), amodiaquine (AQ), mefloquine (MQ), quinine (QN) and artesunate (AS).
Material and methods. Patients with only P. falciparum infection (parasitemia=1,000 rings/µl) were included. Each antimalaria drug was tested with 7 dilutions, two-fold doses, with 2 replications and its effect evaluated using the histidine-rich protein (HRP-2) antigen detection method. Controls included FCB2 (chloroquine-resistant) and NF54 (chloroquine-sensitive) strains. IC50>100, 80, 64, 500 and 10.5 nM were used as the threshold criteria of resistance to CQ, AQ, MQ, QN and AS, respectively.
Results. Twenty-five isolates were evaluated from Urabá (18), Bajo Cauca (2) and the Pacific Coast (5). The mean IC50 obtained with CQ, AQ, MQ, QN and AS were 422.9; 131.4; 56.3; 269.7 and 1.9 nM, respectively, and the number of resistant isolates for these drugs was 19 (76%), 4 (16%), 8 (32%), 6 (24%) and 1 (4%), respectively.
Conclusions. The low sensitivity to CQ found here agrees with both in vitro and in vivo studies in Colombia. Ninety-six percent of the isolates were sensitive to AS. However, this study and previous reports have found isolates with low sensitivity to artemisinines (IC50>10.5 nM). This suggests that the indiscriminate use of these drugs put their efficacy at risk and eventually leave no options for falciparum malaria treatment.
Downloads
Download data is not yet available.
References
1. Bloland P. Drug resistance malaria. Malaria Epidemiology Branch. Centers for Disease Control and Prevention. WHO/CDS/CSR/DRS/2001. Chamblee, GA: World Health Organization; 2001.
2. Ringwald P. Susceptibility of Plasmodium falciparum to antimalarial drugs. Report on global monitoring 1996-2004. WHO/HTM/MAL/2005.1103. Geneve: World Health Organization; 2005.
3. Kaddouri H, Nakache S, Houzé S, Mentré F, Le Bras J. Assessment of the drug susceptibility of Plasmodium falciparum clinical isolates from Africa by using a Plasmodium lactate dehydrogenase immunodetection assay and an inhibitory maximum effect model for precise measurement of the 50-percent inhibitory concentration. Antimicrob Agents Chemother. 2006;50: 3343-9.
4. Zambrano P. Enfermedades transmitidas por vectores (ETV). Informe final de malaria, semanas 1 a 52 Colombia, 2005. Inf Quinc Epidemiol Nac. 2006;11:49-64.
5. OMS. Evaluación de la eficacia terapéutica de los medicamentos para el tratamiento del paludismo por Plasmodium falciparum sin complicaciones en las Américas. OPS/HCP/HCT/113/98. Washington: Organización Mundial de la Salud; 1998.
6. WHO. Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. WHO/HTM/RBM/2003.50. Geneva: World Health Organization; 2003.
7. Blair S, Carmona-Fonseca J, Pineros JG, Ríos A, Álvarez T, Álvarez G, et al. Therapeutic efficacy test in malaria falciparum in Antioquia, Colombia. Malar J. 2006;5:14
8. Espinal C, Moreno E, Guerra P, De la Vega P. Aislamiento y caracterización de cepas colombianas de Plasmodium falciparum. Biomédica. 1982;2:118-28.
9. Arias A, Espinal C, Guerra P, Cortés G. In vitro and in vivo susceptibilities of P. falciparum to antimalarial drugs in some regions of Colombia. Acta Med Colomb. 1982;7:385.
10. Espinal CA, Cortés GT, Guerra P, Arias AE. Sensitivity of Plasmodium falciparum to antimalarial drugs in Colombia. Am J Trop Med Hyg. 1985;34:675-80.
11. Blair S, Lacharme LL, Fonseca JC, Tobón A. Resistance of Plasmodium falciparum to 3 antimalarials in Turbo (Antioquia, Colombia), 1998. Rev Panam Salud Pública. 2001;9:23-9.
12. Blair S, Lacharme LL, Carmona J, Tobón A. Resistance of P. falciparum to antimalarial drugs en Zaragoza (Antioquia, Colombia). Mem Inst Oswaldo Cruz. 2002;97:401-6.
13. González IJ, Varela RE, Murillo C, Ferro BE, Salas J, Giraldo LE, et al. Polymorphisms in cg2 and pfcrt genes and resistance to chloroquine and other antimalarials in vitro in Plasmodium falciparum isolates from Colombia. Trans R Soc Trop Med Hyg. 2003;97: 318-24.
14. Noedl H, Wongsrichanalai C, Wernsdorfer WH. Malaria drug-sensitivity testing: new assays, new perspectives. Trends Parasitol. 2003;19:175-81.
15. Noedl H, Wernsdorfer WH, Miller RS, Wongsrichanalai C. Histidine-rich protein II: a novel approach to malaria drug sensitivity testing. Antimicrob Agents Chemother. 2002;46:1658-64.
16. Noedl H, Wernsdorfer WH, Kollaritsch H, Looareesuwan S, Miller RS, Wongsrichanalai C. Malaria drug-susceptibility testing. HRP-2-based assays: current data, future perspectives. Wien Klin Wochenschr. 2003;115(Suppl.3):23-7.
17. Noedl H, Attlmayr B, Wernsdorfer WH, Kollaritsch H, Miller RS. A histidine-rich protein 2-based malaria drug sensitivity assay for field use. Am J Trop Med Hyg. 2004;71:711-4.
18. Noedl H. Malaria. Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS, Bangkok, Thailand) Consultado: marzo de 2006. Disponible en: www.malaria.farch.net
19. Ljungström I, Perlmann H, Schlichtherle M, Scherf A, Wahlgren M. Methods in malaria research. Manassas, Virginia: Malaria Research and Reference Reagent Resource Center (MR4); 2004.
20. Ponnudurai T, Leeuwenberg AD, Meuwissen JH. Chloroquine sensitivity of isolates of Plasmodium falciparum adapted to in vitro culture. Trop Geog Med. 1981;33:50-4.
21. Moreno C. Actividad antiplasmodial in vitro de plantas del género Piper (tesis). Medellín: Universidad de Antioquia; 2005.
22. WHO. In vitro micro-test (Mark III) for the assessment of the response of Plasmodium falciparum to chloroquine, mefloquine, quinine, amodiaquine, sulfadoxine/pyrimethamine and artemisinin. Instructions for use of the in vitro micro-test kit (Mark III). CTC/MAL/97.20 Rev.2. Geneva: World Health Organization, Division of Control of Tropical Diseases; 2001.
23. Cerutti Junior C, Marques C, Alencar FE, Durlacher RR, Alween A, Segurado AA, et al. Antimalarial drug susceptibility testing of Plasmodium falciparum in Brazil using a radioisotope method. Mem Inst Oswaldo Cruz. 1999;94:803-9.
24. Pradines B, Tall A, Rogier C, Spiegel A, Mosnier J, Marrama L, et al. In vitro activities of ferro-chloroquine against 55 Senegalese isolates of Plasmodium falciparum in comparison with those of standard antimalarial drugs. Trop Med Int Health. 2002;7: 265-70.
25. Wongsrichanalai C, Lin K, Pang LW, Faiz MA, Noedl H, Wimonwattrawatee T, et al. In vitro susceptibility of Plasmodium falciparum isolates from Myanmar to antimalarial drugs. Am J Trop Med Hyg. 2001;65:450-5.
26. Rahman NN. Evaluation of the sensitivity in vitro of Plasmodium falciparum and in vivo of Plasmodium chabaudi Malaria to various drugs and their combinations. Med J Malaysia. 1997;52:390-8.
27. Kayser O, Kiderlen AF, Brun R. In vitro activity of aurones against Plasmodium falciparum strains K1 and NF54. Planta Med. 2001;67:718-21.
28. Garavito G, Rincon J, Arteaga L, Hata Y, Bourdy G, Gimenez A, et al. Antimalarial activity of some Colombian medicinal plants. J Ethnopharmacol. 2006; 107:460-2.
29. Aubouy A, Mayombo J, Keundjian A, Bakary M, Le Bras J, Deloron P. Short report: lack of prediction of amodiaquine efficacy in treating Plasmodium falciparum malaria by in vitro tests. Am J Trop Med Hyg. 2004;71:294-6.
30. Brasseur P, Agnamey P, Ekobo AS, Samba G, Favennec L, Kouamouo J. Sensitivity of Plasmodium falciparum to amodiaquine and chloroquine in central Africa: a comparative study in vivo and in vitro. Trans R Soc Trop Med Hyg. 1995;89:528-30.
31. Tinto H, Rwagacondo C, Karema C, Mupfasoni D, Vandoren W, Rusanganwa E, et al. In-vitro susceptibility of Plasmodium falciparum to monodese-thylamodiaquine, dihydroartemisinin and quinine in an area of high chloroquine resistance in Rwanda. Trans R Soc Trop Med Hyg. 2006;100:509-14.
32. Mount DL, Patchen LC, Nguyen-Dinh P, Barber AM, Schwartz IK, Churchill FC. Sensitive analysis of blood for amodiaquine and three metabolites by high-performance liquid chromatography with electro-chemical detection. J Chromatogr. 1986;383:375-86.
33. Brasseur P, Guiguemde R, Diallo S, Guiyedi V, Kombila M, Ringwald P, et al. Amodiaquine remains effective for treating uncomplicated malaria in west and central Africa. Trans R Soc Trop Med Hyg. 1999;93: 645-50.
34. Gorissen E, Ashruf G, Lamboo M, Bennebroek J, Gikunda S, Mbaruku G, et al. In vivo efficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi, Kenya and Kigoma, Tanzania. Trop Med Int Health. 2000; 5:459-63.
35. Gonzalez I, Padilla J, Giraldo L, Saravia N. Eficacia de amodiaquina y sulfadoxina/pirimetamina en el tratamiento de malaria no complicada por Plasmodium falciparum en Nariño, Colombia, 1999-2002. Biomédica. 2003;23:38-46.
36. Ong CE, Coulter S, Birkett DJ, Bhasker CR, Miners JO. The xenobiotic inhibitor profile of cytochrome P4502C8. Br J Clin Pharmacol. 2000;50:573-80.
37. Dai D, Tang J, Rose R, Hodgson E, Bienstock RJ, Mohrenweiser HW, et al. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther. 2001;299:825-31.
38. Dai D, Zeldin DC, Blaisdell JA, Chanas B, Coulter SJ, Ghanayem BI, et al. Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid. Pharmacogenetics. 2001;11:597-607.
39. Guzmán V. Respuesta terapéutica a la mefloquina y la amodiaquina según el CYP450 y el estado nutricional de pacientes con malaria falciparum (tesis). Medellín: Universidad de Antioquia; 2005.
40. Ministerio de Salud. Resolución No. 00412 de 2000. Guía de atención clínica para el diagnóstico y tratamiento de la malaria. Bogotá: Ministerio de Salud: 2000.
41. Jambou R, Legrand E, Niang M, Khim N, Lim P, Volney B, et al. Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet. 2005;366:1960-3.
2. Ringwald P. Susceptibility of Plasmodium falciparum to antimalarial drugs. Report on global monitoring 1996-2004. WHO/HTM/MAL/2005.1103. Geneve: World Health Organization; 2005.
3. Kaddouri H, Nakache S, Houzé S, Mentré F, Le Bras J. Assessment of the drug susceptibility of Plasmodium falciparum clinical isolates from Africa by using a Plasmodium lactate dehydrogenase immunodetection assay and an inhibitory maximum effect model for precise measurement of the 50-percent inhibitory concentration. Antimicrob Agents Chemother. 2006;50: 3343-9.
4. Zambrano P. Enfermedades transmitidas por vectores (ETV). Informe final de malaria, semanas 1 a 52 Colombia, 2005. Inf Quinc Epidemiol Nac. 2006;11:49-64.
5. OMS. Evaluación de la eficacia terapéutica de los medicamentos para el tratamiento del paludismo por Plasmodium falciparum sin complicaciones en las Américas. OPS/HCP/HCT/113/98. Washington: Organización Mundial de la Salud; 1998.
6. WHO. Assessment and monitoring of antimalarial drug efficacy for the treatment of uncomplicated falciparum malaria. WHO/HTM/RBM/2003.50. Geneva: World Health Organization; 2003.
7. Blair S, Carmona-Fonseca J, Pineros JG, Ríos A, Álvarez T, Álvarez G, et al. Therapeutic efficacy test in malaria falciparum in Antioquia, Colombia. Malar J. 2006;5:14
8. Espinal C, Moreno E, Guerra P, De la Vega P. Aislamiento y caracterización de cepas colombianas de Plasmodium falciparum. Biomédica. 1982;2:118-28.
9. Arias A, Espinal C, Guerra P, Cortés G. In vitro and in vivo susceptibilities of P. falciparum to antimalarial drugs in some regions of Colombia. Acta Med Colomb. 1982;7:385.
10. Espinal CA, Cortés GT, Guerra P, Arias AE. Sensitivity of Plasmodium falciparum to antimalarial drugs in Colombia. Am J Trop Med Hyg. 1985;34:675-80.
11. Blair S, Lacharme LL, Fonseca JC, Tobón A. Resistance of Plasmodium falciparum to 3 antimalarials in Turbo (Antioquia, Colombia), 1998. Rev Panam Salud Pública. 2001;9:23-9.
12. Blair S, Lacharme LL, Carmona J, Tobón A. Resistance of P. falciparum to antimalarial drugs en Zaragoza (Antioquia, Colombia). Mem Inst Oswaldo Cruz. 2002;97:401-6.
13. González IJ, Varela RE, Murillo C, Ferro BE, Salas J, Giraldo LE, et al. Polymorphisms in cg2 and pfcrt genes and resistance to chloroquine and other antimalarials in vitro in Plasmodium falciparum isolates from Colombia. Trans R Soc Trop Med Hyg. 2003;97: 318-24.
14. Noedl H, Wongsrichanalai C, Wernsdorfer WH. Malaria drug-sensitivity testing: new assays, new perspectives. Trends Parasitol. 2003;19:175-81.
15. Noedl H, Wernsdorfer WH, Miller RS, Wongsrichanalai C. Histidine-rich protein II: a novel approach to malaria drug sensitivity testing. Antimicrob Agents Chemother. 2002;46:1658-64.
16. Noedl H, Wernsdorfer WH, Kollaritsch H, Looareesuwan S, Miller RS, Wongsrichanalai C. Malaria drug-susceptibility testing. HRP-2-based assays: current data, future perspectives. Wien Klin Wochenschr. 2003;115(Suppl.3):23-7.
17. Noedl H, Attlmayr B, Wernsdorfer WH, Kollaritsch H, Miller RS. A histidine-rich protein 2-based malaria drug sensitivity assay for field use. Am J Trop Med Hyg. 2004;71:711-4.
18. Noedl H. Malaria. Department of Immunology and Medicine, Armed Forces Research Institute of Medical Sciences (USAMC-AFRIMS, Bangkok, Thailand) Consultado: marzo de 2006. Disponible en: www.malaria.farch.net
19. Ljungström I, Perlmann H, Schlichtherle M, Scherf A, Wahlgren M. Methods in malaria research. Manassas, Virginia: Malaria Research and Reference Reagent Resource Center (MR4); 2004.
20. Ponnudurai T, Leeuwenberg AD, Meuwissen JH. Chloroquine sensitivity of isolates of Plasmodium falciparum adapted to in vitro culture. Trop Geog Med. 1981;33:50-4.
21. Moreno C. Actividad antiplasmodial in vitro de plantas del género Piper (tesis). Medellín: Universidad de Antioquia; 2005.
22. WHO. In vitro micro-test (Mark III) for the assessment of the response of Plasmodium falciparum to chloroquine, mefloquine, quinine, amodiaquine, sulfadoxine/pyrimethamine and artemisinin. Instructions for use of the in vitro micro-test kit (Mark III). CTC/MAL/97.20 Rev.2. Geneva: World Health Organization, Division of Control of Tropical Diseases; 2001.
23. Cerutti Junior C, Marques C, Alencar FE, Durlacher RR, Alween A, Segurado AA, et al. Antimalarial drug susceptibility testing of Plasmodium falciparum in Brazil using a radioisotope method. Mem Inst Oswaldo Cruz. 1999;94:803-9.
24. Pradines B, Tall A, Rogier C, Spiegel A, Mosnier J, Marrama L, et al. In vitro activities of ferro-chloroquine against 55 Senegalese isolates of Plasmodium falciparum in comparison with those of standard antimalarial drugs. Trop Med Int Health. 2002;7: 265-70.
25. Wongsrichanalai C, Lin K, Pang LW, Faiz MA, Noedl H, Wimonwattrawatee T, et al. In vitro susceptibility of Plasmodium falciparum isolates from Myanmar to antimalarial drugs. Am J Trop Med Hyg. 2001;65:450-5.
26. Rahman NN. Evaluation of the sensitivity in vitro of Plasmodium falciparum and in vivo of Plasmodium chabaudi Malaria to various drugs and their combinations. Med J Malaysia. 1997;52:390-8.
27. Kayser O, Kiderlen AF, Brun R. In vitro activity of aurones against Plasmodium falciparum strains K1 and NF54. Planta Med. 2001;67:718-21.
28. Garavito G, Rincon J, Arteaga L, Hata Y, Bourdy G, Gimenez A, et al. Antimalarial activity of some Colombian medicinal plants. J Ethnopharmacol. 2006; 107:460-2.
29. Aubouy A, Mayombo J, Keundjian A, Bakary M, Le Bras J, Deloron P. Short report: lack of prediction of amodiaquine efficacy in treating Plasmodium falciparum malaria by in vitro tests. Am J Trop Med Hyg. 2004;71:294-6.
30. Brasseur P, Agnamey P, Ekobo AS, Samba G, Favennec L, Kouamouo J. Sensitivity of Plasmodium falciparum to amodiaquine and chloroquine in central Africa: a comparative study in vivo and in vitro. Trans R Soc Trop Med Hyg. 1995;89:528-30.
31. Tinto H, Rwagacondo C, Karema C, Mupfasoni D, Vandoren W, Rusanganwa E, et al. In-vitro susceptibility of Plasmodium falciparum to monodese-thylamodiaquine, dihydroartemisinin and quinine in an area of high chloroquine resistance in Rwanda. Trans R Soc Trop Med Hyg. 2006;100:509-14.
32. Mount DL, Patchen LC, Nguyen-Dinh P, Barber AM, Schwartz IK, Churchill FC. Sensitive analysis of blood for amodiaquine and three metabolites by high-performance liquid chromatography with electro-chemical detection. J Chromatogr. 1986;383:375-86.
33. Brasseur P, Guiguemde R, Diallo S, Guiyedi V, Kombila M, Ringwald P, et al. Amodiaquine remains effective for treating uncomplicated malaria in west and central Africa. Trans R Soc Trop Med Hyg. 1999;93: 645-50.
34. Gorissen E, Ashruf G, Lamboo M, Bennebroek J, Gikunda S, Mbaruku G, et al. In vivo efficacy study of amodiaquine and sulfadoxine/ pyrimethamine in Kibwezi, Kenya and Kigoma, Tanzania. Trop Med Int Health. 2000; 5:459-63.
35. Gonzalez I, Padilla J, Giraldo L, Saravia N. Eficacia de amodiaquina y sulfadoxina/pirimetamina en el tratamiento de malaria no complicada por Plasmodium falciparum en Nariño, Colombia, 1999-2002. Biomédica. 2003;23:38-46.
36. Ong CE, Coulter S, Birkett DJ, Bhasker CR, Miners JO. The xenobiotic inhibitor profile of cytochrome P4502C8. Br J Clin Pharmacol. 2000;50:573-80.
37. Dai D, Tang J, Rose R, Hodgson E, Bienstock RJ, Mohrenweiser HW, et al. Identification of variants of CYP3A4 and characterization of their abilities to metabolize testosterone and chlorpyrifos. J Pharmacol Exp Ther. 2001;299:825-31.
38. Dai D, Zeldin DC, Blaisdell JA, Chanas B, Coulter SJ, Ghanayem BI, et al. Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid. Pharmacogenetics. 2001;11:597-607.
39. Guzmán V. Respuesta terapéutica a la mefloquina y la amodiaquina según el CYP450 y el estado nutricional de pacientes con malaria falciparum (tesis). Medellín: Universidad de Antioquia; 2005.
40. Ministerio de Salud. Resolución No. 00412 de 2000. Guía de atención clínica para el diagnóstico y tratamiento de la malaria. Bogotá: Ministerio de Salud: 2000.
41. Jambou R, Legrand E, Niang M, Khim N, Lim P, Volney B, et al. Resistance of Plasmodium falciparum field isolates to in-vitro artemether and point mutations of the SERCA-type PfATPase6. Lancet. 2005;366:1960-3.
How to Cite
1.
Blair S, Arango E, Carmona Fonseca J. In vitro susceptibility of Colombian Plasmodium falciparum isolates to different antimalarial drugs. biomedica [Internet]. 2008 Jun. 1 [cited 2024 May 11];28(2):213-2. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/92
Some similar items:
- Sandra Milena Barrera, Manuel Alberto Pérez, Angélica Knudson, Rubén Santiago Nicholls, Ángela Patricia Guerra, Genotypic survery of Plasmodium falciparum based on the msp1, msp2 and glurp genes by multiplex PCR , Biomedica: Vol. 30 No. 4 (2010)
- Johanna Ochoa, Lyda Osorio, Epidemiology of urban malaria in Quibdo, Choco. , Biomedica: Vol. 26 No. 2 (2006)
- Manuel Alberto Pérez, Liliana Jazmín Cortés, Ángela Patricia Guerra, Angélica Knudson, Carlos Usta, Rubén Santiago Nicholls, Efficacy of the amodiaquine+sulfadoxine-pyrimethamine combination and of chloroquine for the treatment of malaria in Córdoba, Colombia, 2006 , Biomedica: Vol. 28 No. 1 (2008)
- Alberto Tobón-Castaño, John Edison Betancur, Severe malaria in pregnant women hospitalized between 2010 and 2014 in the Department of Antioquia (Colombia) , Biomedica: Vol. 39 No. 2 (2019)
- Nohora Marcela Mendoza, Marisol García, Liliana Jazmín Cortés, Claudia Vela, Rigoberto Erazo, Pilar Pérez, Olga Lucía Ospina, Javier Darío Burgos, Evaluation of two rapid diagnostic tests, NOW® ICT Malaria Pf/Pv and OptiMAL®, for diagnosis of malaria , Biomedica: Vol. 27 No. 4 (2007)
- Liliana Jazmín Cortés, Lyda Muñoz, Martha Stella Ayala, Comparison of methodologies for microscopic malaria diagnosis , Biomedica: Vol. 38 No. 2 (2018)
- Angela Patricia Guerra, Angélica Knudson, Rubén Santiago Nicholls, John Alexander Galindo, Zaava Ravid, Sonia Rahirant, Nidia Duarte, Jacqueline Chaparro-Olaya, Moisés Wasserman, Genotyping of the Plasmodium falciparum msp1 (block 2) and dhfr (codon 108) genes in field samples collected in four endemic Colombian localities. , Biomedica: Vol. 26 No. 1 (2006)
- John Alexander Galindo, Fabio Aníbal Cristiano, Angélica Knudson, Rubén Santiago Nicholls, Ángela Patricia Guerra, Point mutations in dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum from three endemic malaria regions in Colombia , Biomedica: Vol. 30 No. 1 (2010)
- Amanda Maestre, Jaime Carmona-Fonseca, Amanda Maestre, Alta frecuencia de mutaciones puntuales en pfcrt de Plasmodium falciparum y emergencia de nuevos haplotipos mutantes en Colombia , Biomedica: Vol. 28 No. 4 (2008)
- Jaime E. Bernal, Martha Lucía Tamayo , Ignacio Briceño , Escilda Benavides , Newborn screening in Colombia: The experience of a private program in Bogotá , Biomedica: Vol. 44 No. 1 (2024)
Issue
Section
Original articles
| Article metrics | |
|---|---|
| Abstract views | |
| Galley vies | |
| PDF Views | |
| HTML views | |
| Other views | |
