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Inicio Enfermedades Infecciosas y Microbiología Clínica Vacuna frente a la malaria: el gran reto para los países en vías de desarrollo
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Vol. 26. Issue S1.
Vacunas: presente y futuro
Pages 86-95 (January 2008)
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Vol. 26. Issue S1.
Vacunas: presente y futuro
Pages 86-95 (January 2008)
Vacunas: presente y futuro
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Vacuna frente a la malaria: el gran reto para los países en vías de desarrollo
Malaria vaccine: the main challenge for developing countries
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Montserrat Renom Lloncha,b, Sarah Lafuente van der Sluisa,
Corresponding author
slafuent@clinic.ub.es

Correspondencia: Dra. S. Lafuente van der Sluis. CRESIB. Rosselló, 132, 4ª planta. 08036 Barcelona. España.
, Pedro Luis Alonso Fernándeza,b
a Centre de Recerca en Salut Internacional de Barcelona (CRESIB). Hospital Clínic/IDIBAPS. Universitat de Barcelona. Barcelona. España
b Centro de Investigação em Saúde da Manhiça (CISM). Maputo. Mozambique
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La malaria, enfermedad causada por parásitos protozoarios del género Plasmodium, representa uno de los problemas más graves de salud pública en el mundo y es la enfermedad parasitaria más importante en humanos. Se estima que unos 3.000 millones de personas están expuestas a la enfermedad al vivir en zonas endémicas, y cada año ocurren entre 300-500 millones de episodios clínicos de los cuales aproximadamente 1-3 millones mueren, la mayoría niños menores de 5 años. A pesar de ser una enfermedad endémica en varios continentes, es en África, y especialmente en los territorios comprendidos entre los 2 trópicos, donde se acumula hasta un 90% de las muertes, casi siempre en niños menores de 5 años. Existen diferentes y complementarias herramientas disponibles para controlar la enfermedad, entre las que destacan las siguientes: el diagnóstico e inicio rápido del tratamiento de los casos con un antimalárico eficaz, la disminución del contacto entre hombre y vector, fundamentalmente con redes mosquiteras impregnadas de insecticida, el tratamiento preventivo intermitente en niños y mujeres embarazadas, y el control del vector mediante fumigación intradomiciliaria o larvicidas. Sin embargo, la implementación de estos mecanismos de control sigue siendo incompleta en la mayoría de las zonas endémicas. Una vacuna eficaz y segura en niños y de bajo coste, sumado a las demás medidas de control ya existentes, sería un elemento clave en el control de la enfermedad. La vacuna que se encuentra en fases más avanzadas de investigación es la compuesta por un antígeno preeritrocítico CSP, llamado RTS,S. Esta vacuna demostró seguridad, immunogenicidad y eficacia en niños de un área rural de Mozambique. Los enormes progresos que se han hecho en los últimos años, junto con unos primeros resultados muy esperanzadores, permiten un optimismo razonable acerca del desarrollo de una vacuna en un futuro próximo.

Palabras clave:
Vacuna
Malaria
Ensayo clínico

Malaria, which is caused by protozoan parasites of the Plasmodium genus, is one of the most serious public health problems worldwide and is the most important parasitic infection in humans. Approximately 3,000 million people are estimated to be exposed to the disease by living in endemic areas. Every year, there are between 300 and 500 million clinical episodes, causing approximately 1-3 million deaths, mainly in children aged less than 5 years. Although malaria is endemic in several continents, 90% of deaths occur in Africa, especially in the regions between the two tropics, and most of those who die are young children. Several tools, which are complementary, are available to control the disease, notable among which are the following: diagnosis and prompt treatment with an effective antimalarial agent, reduction of contact between humans and vector -mainly through the use of insecticideimpregnated mosquito nets-, intermittent preventive treatment in children and pregnant women, and vector control through fumigation in the home or the use of larvicides. However, the implementation of these control measures continues to be incomplete in most endemic areas. In addition to already existing control measures, a safe, effective and lowcost vaccine in children would be a key element in controlling the disease. The vaccine in the most advanced phases of research is that composed by a preerythrocytic antigen, circumsporozoite protein (CSP), called RTS,S. This vaccine has been shown to be safe, immunogenic and effective in children in a rural area of Mozambique. Given the huge advances that have taken place in the last few years, together with highly encouraging initial results, optimism about the development of a vaccine in the near future is reasonable.

Key words:
Vaccine
Malaria
Clinical trial
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Bibliografía
[1.]
R.W. Snow, S.I. Hay.
Comparing methods of estimating the global morbidity burden from Plasmodium falciparum malaria.
Am J Trop Med Hyg, 74 (2006), pp. 189-190
[2.]
J.G. Breman.
The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden.
Am J Trop Med Hyg, 64 (2001), pp. 1-11
[3.]
J.G. Breman, M.S. Alilio, A. Mills.
Conquering the intolerable burden of malaria: what's new, what's needed: a summary.
Am J Trop Med Hyg, 71 (2004), pp. 1-15
[4.]
C. Guinovart, M.M. Navia, M. Tanner, P.L. Alonso.
Malaria: burden of disease.
Curr Mol Med, 6 (2006), pp. 137-140
[5.]
S.I. Hay, C.A. Guerra, A.J. Tatem, A.M. Noor, R.W. Snow.
The global distribution and population at risk of malaria: past, present, and future.
Lancet Infect Dis, 4 (2004), pp. 327-336
[6.]
N.J. White.
Malaria.
Manson's tropical diseases, 21st ed., pp. 1205-1295
[7.]
M. Prudencio, A. Rodriguez, M.M. Mota.
The silent path to thousands of merozoites: the Plasmodium liver stage.
Nat Rev Microbiol, 4 (2006), pp. 849-856
[8.]
WHO. Guidelines for the treatment of malaria. 2006.
[9.]
P. Trouiller, P. Olliaro, E. Torreele, J. Orbinski, R. Laing, N. Ford.
Drug development for neglected diseases: a deficient market and a public-health policy failure.
Lancet, 359 (2002), pp. 2188-2194
[10.]
D.F. Clyde.
Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites.
Am J Trop Med Hyg, 24 (1975), pp. 397-401
[11.]
J.B. Dame, J.L. Williams, T.F. McCutchan, J.L. Weber, R.A. Wirtz, W.T. Hockmeyer, et al.
Structure of the gene encoding the immunodominant surface antigen on the sporozoite of the human malaria parasite Plasmodium falciparum.
Science, 225 (1984), pp. 593-599
[12.]
P.L. Alonso, J. Sacarlal, J.J. Aponte, A. Leach, E. Macete, P. Aide, et al.
Duration of protection with RTS,S/AS02A malaria vaccine in prevention of Plasmodium falciparum disease in Mozambican children: single-blind extended follow- up of a randomised controlled trial.
Lancet, 366 (2005), pp. 2012-2018
[13.]
S. Gupta, R.W. Snow, C.A. Donnelly, K. Marsh, C. Newbold.
Immunity to non-cerebral severe malaria is acquired after one or two infections.
Nat Med, 5 (1999), pp. 340-343
[14.]
J.K. Baird, R.W. Snow.
Acquired immunity in a holoendemic setting of Plasmodium falciparum and P.vivax malaria.
Am J Trop Med Hyg, 76 (2007), pp. 995-996
[15.]
D. Webster, A.V. Hill.
Progress with new malaria vaccines.
Bull World Health Organ, 81 (2003), pp. 902-909
[16.]
D. Raghunath.
Malaria vaccine: are we anywhere close?.
J Postgrad Med, 50 (2004), pp. 51-54
[17.]
J.F. Trape, C. Rogier, L. Konate, N. Diagne, H. Bouganali, B. Canque, et al.
The Dielmo project: a longitudinal study of natural malaria infection and the mechanisms of protective immunity in a community living in a holoendemic area of Senegal.
Am J Trop Med Hyg, 51 (1994), pp. 123-137
[18.]
J.K. Baird.
Age-dependent characteristics of protection v. susceptibility to Plasmodium falciparum.
Ann Trop Med Parasitol, 92 (1998), pp. 367-390
[19.]
W.R. Ballou, M. Arevalo-Herrera, D. Carucci, T.L. Richie, G. Corradin, C. Diggs, et al.
Update on the clinical development of candidate malaria vaccines.
Am J Trop Med Hyg, 71 (2004), pp. 239-247
[20.]
A. Sabchareon, T. Burnouf, D. Ouattara, P. Attanath, H. Bouharoun-Tayoun, P. Chantavanich, et al.
Parasitologic and clinical human response to immunoglobulin administration in falciparum malaria.
Am J Trop Med Hyg, 45 (1991), pp. 297-308
[21.]
K.H. Rieckmann, R.L. Beaudoin, J.S. Cassells, K.W. Sell.
Use of attenuated sporozoites in the immunization of human volunteers against falciparum malaria.
Bull World Health Organ, 57 (1979), pp. 261-265
[22.]
A.K. Mueller, M. Labaied, S.H. Kappe, K. Matuschewski.
Genetically modified Plasmodium parasites as a protective experimental malaria vaccine.
Nature, 433 (2005), pp. 164-167
[23.]
B. Greenwood.
Malaria vaccines. Evaluation and implementation.
Acta Trop, 23 (2005), pp. 534-542
[24.]
B. Greenwood, P. Alonso.
Malaria vaccine trials.
Chem Immunol, 80 (2002), pp. 366-395
[25.]
C.C. Hermsen, S.J. De Vlas, G.J. Van Gemert, D.S. Telgt, D.F. Verhage, R.W. Sauerwein.
Testing vaccines in human experimental malaria: statistical analysis of parasitemia measured by a quantitative real-time polymerase chain reaction.
Am J Trop Med Hyg, 71 (2004), pp. 196-201
[26.]
Q. Cheng, G. Lawrence, C. Reed, A. Stowers, L. Ranford-Cartwright, A. Creasey, et al.
Measurement of Plasmodium falciparum growth rates in vivo: a test of malaria vaccines.
Am J Trop Med Hyg, 57 (1997), pp. 495-500
[27.]
B.M. Greenwood, P.H. David, L.N. Otoo-Forbes, S.J. Allen, P.L. Alonso, J.R. Armstrong Schellenberg, et al.
Mortality and morbidity from malaria after stopping malaria chemoprophylaxis.
Trans R Soc Trop Med Hyg, 89 (1995), pp. 629-633
[28.]
C. Menéndez, E. Kahigwa, R. Hirt, P. Vounatsou, J.J. Aponte, F. Font, et al.
Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants.
[29.]
D.G. Heppner Jr, K.E. Kester, C.F. Ockenhouse, N. Tornieporth, O. Ofori, J.A. Lyon, et al.
Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research.
Vaccine, 23 (2005), pp. 2243-2250
[30.]
K.A. Bojang, P.J. Milligan, M. Pinder, L. Vigneron, A. Alloueche, K.E. Kester, et al.
Efficacy of RTS,S/AS02 malaria vaccine against Plasmodium falciparum infection in semi-immune adult men in The Gambia: a randomised trial.
Lancet, 358 (2001), pp. 1927-1934
[31.]
P.L. Alonso, J. Sacarlal, J.J. Aponte, A. Leach, E. Macete, J. Milman, et al.
Efficacy of the RTS,S/AS02A vaccine against Plasmodium falciparum infection and disease in young African children: randomised controlled trial.
Lancet, 364 (2004), pp. 1411-1420
[32.]
V.A. Stewart, S.M. McGrath, D.S. Walsh, S. Davis, A.S. Hess, L.A. Ware, et al.
Preclinical evaluation of new adjuvant formulations to improve the immunogenicity of the malaria vaccine RTS,S/AS02A.
Vaccine, 24 (2006), pp. 6483-6492
[33.]
N. Maire, F. Tediosi, A. Ross, T. Smith.
Predictions of the epidemiologic impact of introducing a pre-erythrocytic vaccine into the expanded program on immunization in sub-Saharan Africa.
Am J Trop Med Hyg, 75 (2006), pp. 111-118
[34.]
E. Angov, B.M. Aufiero, A.M. Turgeon, M. Van Handenhove, C.F. Ockenhouse, K.E. Kester, et al.
Development and pre-clinical analysis of a Plasmodium falciparum merozoite surface protein-1(42) malaria vaccine.
Mol Biochem Parasitol, 128 (2003), pp. 195-204
[35.]
M.A. Thera, O.K. Doumbo, D. Coulibaly, D.A. Diallo, I. Sagara, A. Dicko, et al.
Safety and allele-specific immunogenicity of a malaria vaccine in malian adults: results of a phase I randomized trial.
PLoS Clin Trials, 1 (2006), pp. 34e
[36.]
J.A. Stoute, J. Gombe, M.R. Withers, J. Siangla, D. McKinney, M. Onyango, et al.
Phase 1 randomized double-blind safety and immunogenicity trial of Plasmodium falciparum malaria merozoite surface protein FMP1 vaccine, adjuvanted with AS02A, in adults in western Kenya.
[37.]
M.R. Withers, D. McKinney, B.R. Ogutu, J.N. Waitumbi, J.B. Milman, O.J. Apollo, et al.
Safety and reactogenicity of an MSP-1 malaria vaccine candidate: a randomized phase Ib dose-escalation trial in Kenyan children.
PLoS Clin Trials, 1 (2006), pp. 32e
[38.]
O. Silvie, J.F. Franetich, S. Charrin, M.S. Mueller, A. Siau, M. Bodescot, et al.
A role for apical membrane antigen 1 during invasion of hepatocytes by Plasmodium falciparum sporozoites.
J Biol Chem, 279 (2004), pp. 9490-9496
[39.]
R. Carter, K.N. Mendis, L.H. Miller, L. Molineaux, A. Saul.
Malaria transmission- blocking vaccines—how can their development be supported?.
Nat Med, 6 (2000), pp. 241-244
[40.]
T. Arakawa, A. Komesu, H. Otsuki, J. Sattabongkot, R. Udomsangpetch, Y. Matsumoto, et al.
Nasal immunization with a malaria transmission-blocking vaccine candidate, Pfs25, induces complete protective immunity in mice against field isolates of Plasmodium falciparum.
Infect Immunol, 73 (2005), pp. 7375-7380
[41.]
L. Schofield, M.C. Hewitt, K. Evans, M.A. Siomos, P.H. Seeberger.
Synthetic GPI as a candidate anti-toxic vaccine in a model of malaria.
Nature, 418 (2002), pp. 785-789
[42.]
L. Schofield.
Rational approaches to developing an anti-disease vaccine against malaria.
Microbes Infect, 9 (2007), pp. 784-791
[43.]
S.L. Hoffman, L.M. Goh, T.C. Luke, I. Schneider, T.P. Le, D.L. Doolan, et al.
Protection of humans against malaria by immunization with radiation-attenuated Plasmodium falciparum sporozoites.
J Infect Dis, 185 (2002), pp. 1155-1164
[44.]
T.C. Luke, S.L. Hoffman.
Rationale and plans for developing a non-replicating, metabolically active, radiation-attenuated Plasmodium falciparum sporozoite vaccine.
J Exp Biol, 206 (2003), pp. 3803-3808
[45.]
M. Wykes, M.F. Good.
A case for whole-parasite malaria vaccines.
Int J Parasitol, 37 (2007), pp. 705-712
[46.]
D.J. Pombo, G. Lawrence, C. Hirunpetcharat, C. Rzepczyk, M. Bryden, N. Cloonan, et al.
Immunity to malaria after administration of ultra-low doses of red cells infected with Plasmodium falciparum.
[47.]
K. Mendis, B.J. Sina, P. Marchesini, R. Carter.
The neglected burden of Plasmodium vivax malaria.
Am J Trop Med Hyg, 64 (2001), pp. 97-106
[48.]
S. Herrera, G. Corradin, M. Arevalo-Herrera.
An update on the search for a Plasmodium vivax vaccine.
Trends Parasitol, 23 (2007), pp. 122-128
[49.]
E.M. Malkin, A.P. Durbin, D.J. Diemert, J. Sattabongkot, Y. Wu, K. Miura, et al.
Phase 1 vaccine trial of Pvs25H: a transmission blocking vaccine for Plasmodium vivax malaria.
Vaccine, 23 (2005), pp. 3131-3138
[50.]
S. Herrera, A. Bonelo, B.L. Perlaza, O.L. Fernández, L. Victoria, A.M. Lenis, et al.
Safety and elicitation of humoral and cellular responses in colombian malaria- naive volunteers by a Plasmodium vivax circumsporozoite protein-derived synthetic vaccine.
Am J Trop Med Hyg, 73 (2005), pp. 3-9
[51.]
S.S. Yazdani, P. Mukherjee, V.S. Chauhan, C.E. Chitnis.
Immune responses to asexual blood-stages of malaria parasites.
Curr Mol Med, 6 (2006), pp. 187-203
[52.]
K.L. Perera, S.M. Handunnetti, I. Holm, S. Longacre, K. Mendis.
Baculovirus merozoite surface protein 1 C-terminal recombinant antigens are highly protective in a natural primate model for human Plasmodium vivax malaria.
Infect Immunol, 66 (1998), pp. 1500-1506
[53.]
C. Menéndez, J. Ordi, M.R. Ismail, P.J. Ventura, J.J. Aponte, E. Kahigwa, et al.
The impact of placental malaria on gestational age and birth weight.
J Infect Dis, 181 (2000), pp. 1740-1745
[54.]
S.J. Rogerson, L. Hviid, P.E. Duffy, R.F. Leke, D.W. Taylor.
Malaria in pregnancy: pathogenesis and immunity.
Lancet Infect Dis, 7 (2007), pp. 105-117
[55.]
A. Salanti, M. Dahlback, L. Turner, M.A. Nielsen, L. Barfod, P. Magistrado, et al.
Evidence for the involvement of VAR2CSA in pregnancy-associated malaria.
J Exp Med, 200 (2004), pp. 1197-1203
[56.]
B. Gamain, J.D. Smith, N.K. Viebig, J. Gysin, A. Scherf.
Pregnancy-associated malaria: parasite binding, natural immunity and vaccine development.
Int J Parasitol, 37 (2007), pp. 273-283
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