Adjei GO, Kurtzhals JA, Rodrigues OP, Alifrangis M, Hoegberg LC, Kitcher ED, Badoe EV, Lamptey R, Goka BQ, 2008. Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up. Malar J 7: 127.
Tangpukdee N, Yew HS, Krudsood S, Punyapradit N, Somwong W, Looareesuwan S, Kano S, Wilairatana P, 2008. Dynamic changes in white blood cell counts in uncomplicated Plasmodium falciparum and P. vivax malaria. Parasitol Int 57: 490–494.
Erhart LM, Yingyuen K, Chuanak N, Buathong N, Laoboonchai A, Miller RS, Meshnick SR, Gasser RA Jr, Wongsrichanalai C, 2004. Hematologic and clinical indices of malaria in a semi-immune population of western Thailand. Am J Trop Med Hyg 70: 8–14.
Taylor WR, Widjaja H, Basri H, Ohrt C, Taufik T, Tjitra E, Baso S, Fryauff D, Hoffman SL, Richie TL, 2008. Changes in the total leukocyte and platelet counts in Papuan and non Papuan adults from northeast Papua infected with acute Plasmodium vivax or uncomplicated Plasmodium falciparum malaria. Malar J 7: 259.
Tan SO, McGready R, Zwang J, Pimanpanarak M, Sriprawat K, Thwai KL, Moo Y, Ashley EA, Edwards B, Singhasivanon P, White NJ, Nosten F, 2008. Thrombocytopaenia in pregnant women with malaria on the Thai-Burmese border. Malar J 7: 209.
Adjuik M, Agnamey P, Babiker A, Borrmann S, Brasseur P, Cisse M, Cobelens F, Diallo S, Faucher JF, Garner P, Gikunda S, Kremsner PG, Krishna S, Lell B, Loolpapit M, Matsiegui PB, Missinou MA, Mwanza J, Ntoumi F, Olliaro P, Osimbo P, Rezbach P, Some E, Taylor WR, 2002. Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomized, multicentre trial. Lancet 359: 1365–1372.
Djimdé AA, Fofana B, Sagara I, Sidibe B, Toure S, Dembele D, Dama S, Ouologuem D, Dicko A, Doumbo OK, 2008. Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali. Am J Trop Med Hyg 78: 455–461.
Dorsey G, Staedke S, Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Dokomajilar C, Kamya MR, Rosenthal PJ, 2007. Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. JAMA 297: 2210–2219.
Karema C, Fanello CI, van Overmeir C, van Geertruyden JP, van Doren W, Ngamije D, D'Alessandro U, 2006. Safety and efficacy of dihydroartemisinin/piperaquine (Artekin) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwandan children. Trans R Soc Trop Med Hyg 100: 1105–1111.
Martensson A, Stromberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, Olliaro P, Ali AS, Björkman A, 2005. Efficacy of artesunate plus amodiaquine versus that of artemether-lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania. Clin Infect Dis 41: 1079–1086.
Ndiaye JL, Randrianarivelojosia M, Sagara I, Brasseur P, Ndiaye I, Faye B, Randrianasolo L, Ratsimbasoa A, Forlemu D, Moor VA, Traore A, Niawanlou Dara YD, Lameyre V, Diallo M, Djimde A, Same-Ekobo A, Gaye O, 2009. Randomized, multicentre assessment of the efficacy and safety of ASAQ – a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria. Malar J 8: 125.
Sirima SB, Tiono AB, Gansane A, Diarra A, Ouedraogo A, Konate AT, Kiechel JR, Morgan CC, Olliaro PL, Taylor WR, 2009. The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum. Malar J 8: 48.
Zwang J, Olliaro P, Barennes H, Bonnet M, Brasseur P, Bukirwa H, Cohuet S, D'Alessandro U, Djimdé A, Karema C, Guthmann JP, Hamour S, Ndiaye JL, Mårtensson A, Rwagacondo C, Sagara I, Same-Ekobo A, Sirima SB, van den Broek I, Yeka A, Taylor WR, Dorsey G, Randrianarivelojosia M, 2009. Efficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis. Malar J 8: 203.
Olliaro P, Djimdé A, Karema C, Mårtensson A, Ndiaye JL, Sirima SB, Dorsey G, Zwang J, 2011. Estimated versus actual parasitaemia in acute uncomplicated Plasmodium falciparum malaria in African children under five. Trop Med Int Health 16: 551–554.
Breusch TS, Pagan AR, 1980. The Lagrange multiplier test and its applications to model specification in econometrics. Rev Econ Stud 47: 239–253.
NIAID, 2007. Division of Microbiology and Infectious Diseases Pediatric Toxicity Tables. Available at: http://www.niaid.nih.gov. Accessed June 23, 2010.
McKenzie FE, Prudhomme WA, Magill AJ, Forney JR, Permpanich B, Lucas C, Gasser RA Jr, Wongsrichanalai C, 2005. White blood cell counts and malaria. J Infect Dis 192: 323–330.
Quintó L, Aponte JJ, Sacarlal J, Espasa M, Aide P, Mandomando I, Guinovart C, Macete E, Navia MM, Thompson R, Menéndez C, Alonso PL, 2006. Haematological and biochemical indices in young African children: in search of reference intervals. Trop Med Int Health 11: 1741–1748.
Jadhav UM, Singhvi R, Shah R, 2003. Prognostic implications of white cell differential count and white cell morphology in malaria. J Postgrad Med 49: 218–220.
Ladhani S, Lowe B, Cole AO, Kowuondo K, Newton CR, 2002. Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome. Br J Haematol 119: 839–847.
Sowunmi A, Akindele JA, Balogun MA, 1995. Leukocyte counts in falciparum malaria in African children from an endemic area. Afr J Med Sci 24: 145–149.
Gasasira AF, Kamya MR, Achan J, Mebrahtu T, Kalyango JN, Ruel T, Charlebois E, Staedke SG, Kekitiinwa A, Rosenthal PJ, Havlir D, Dorsey G, 2008. High risk of neutropenia in HIV-infected children following treatment with artesunate plus amodiaquine for uncomplicated malaria in Uganda. Clin Infect Dis 46: 985–991.
Dorsey G, Gasasira AF, Machekano R, Kamya MR, Staedke SG, Hubbard A, 2004. The impact of age, temperature, and parasite density on treatment outcomes from antimalarial clinical trials in Kampala, Uganda. Am J Trop Med Hyg 71: 531–536.
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Hematologic changes in acute and convalescent uncomplicated Plasmodium falciparum malaria have not been well studied, particularly in young children in Africa. Hematologic data were obtained for 3,044 children less than five years of age in seven randomized controlled trials at 14 sites. Using paired analysis between day 28 and baseline in patients without parasitologic failure as a proxy for malaria-induced effects, we found a statistically significant but clinically modest increase in leukocyte counts (5%) resulting from a larger increase in neutrophils (43%) than the decrease in lymphocytes counts (–16%); levels of hemoglobin and platelets decreased (–13% and –49%, respectively). Multivariate random effects analysis showed trends during follow-up (increased levels of hemoglobin, platelets and lymphocytes, and decreased levels of leukocytes and neutrophils) and identified explanatory variables. The risk of neutropenia increased with follow-up time independent of treatment outcome, and was lower with age, higher baseline parasitemia, and artemisinin combination treatment. These analyses provides information on hematologic variations caused by malaria.
Financial support: Julien Zwang was supported by a grant from the Drugs for Neglected Diseases Initiative for the analysis. This initiative is an independent, not-for-profit product developer in partnership working to research and develop new and improved treatments for neglected diseases. It sponsored one of the trials but had no role in the design and conduct of the analysis or interpretation of results reported in the article.
Disclosure: None of the authors have any conflicts of interest.
Authors' addresses: Piero Olliaro, Special Programme for Research and Training in Tropical Diseases, World Health Organization, Avenue Appia 20, 1211 Geneva 27, Switzerland, E-mail: olliarop@who.int. Abdoulaye Djimdé, Malaria Research and Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine and Pharmacy, University of Bamako, Bamako, Mali, E-mail: adjimde@mrtcbko.org. Grant Dorsey, Division of Infectious Diseases Department of Medicine, University of California, San Francisco, San Francisco CA, E-mail: gdorsey@medsfgh.ucsf.edu. Corine Karema, National Malaria Control Programme, Kigali, Rwanda, E-mail: ckarema@gmail.com. Andreas Mårtensson, Infectious Diseases Unit, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden, E-mail: andreas.martensson@ki.se. Jean-Louis Ndiaye, Department of Parasitology, Faculty of Medicine, University Cheikh Anta Diop, Dakar, Senegal, E-mail: jlndiaye@yahoo.com. Sodiomon B. Sirima, Centre National de Recherche et de Formation sur le Paludisme, Ministère de la Santé, Ouagadougou, Burkina Faso, E-mail: s.sirima.cnlp@fasonet.bf. Michel Vaillant, Clinical Epidemiology and Public Health Unit, Centre for Health Studies, Centre de Recherche Publique-Santé, 1A-B, Rue Thomas Edison L-1445, Strassen, Luxembourg, E-mail: michel.vaillant@crp-sante.lu. Julien Zwang, Drugs for Neglected Diseases Initiative, Geneva, Switzerland, 15 Chemin Louis-Dunant, 1202 Geneva, Switzerland, E-mail: zwang@free.fr.
Reprint requests: Piero Olliaro, Special Programme for Research and Training in Tropical Diseases, World Health Organization, Avenue Appia 20, 1211 Geneva 27, Switzerland, E-mail: olliarop@who.int.
Adjei GO, Kurtzhals JA, Rodrigues OP, Alifrangis M, Hoegberg LC, Kitcher ED, Badoe EV, Lamptey R, Goka BQ, 2008. Amodiaquine-artesunate vs artemether-lumefantrine for uncomplicated malaria in Ghanaian children: a randomized efficacy and safety trial with one year follow-up. Malar J 7: 127.
Tangpukdee N, Yew HS, Krudsood S, Punyapradit N, Somwong W, Looareesuwan S, Kano S, Wilairatana P, 2008. Dynamic changes in white blood cell counts in uncomplicated Plasmodium falciparum and P. vivax malaria. Parasitol Int 57: 490–494.
Erhart LM, Yingyuen K, Chuanak N, Buathong N, Laoboonchai A, Miller RS, Meshnick SR, Gasser RA Jr, Wongsrichanalai C, 2004. Hematologic and clinical indices of malaria in a semi-immune population of western Thailand. Am J Trop Med Hyg 70: 8–14.
Taylor WR, Widjaja H, Basri H, Ohrt C, Taufik T, Tjitra E, Baso S, Fryauff D, Hoffman SL, Richie TL, 2008. Changes in the total leukocyte and platelet counts in Papuan and non Papuan adults from northeast Papua infected with acute Plasmodium vivax or uncomplicated Plasmodium falciparum malaria. Malar J 7: 259.
Tan SO, McGready R, Zwang J, Pimanpanarak M, Sriprawat K, Thwai KL, Moo Y, Ashley EA, Edwards B, Singhasivanon P, White NJ, Nosten F, 2008. Thrombocytopaenia in pregnant women with malaria on the Thai-Burmese border. Malar J 7: 209.
Adjuik M, Agnamey P, Babiker A, Borrmann S, Brasseur P, Cisse M, Cobelens F, Diallo S, Faucher JF, Garner P, Gikunda S, Kremsner PG, Krishna S, Lell B, Loolpapit M, Matsiegui PB, Missinou MA, Mwanza J, Ntoumi F, Olliaro P, Osimbo P, Rezbach P, Some E, Taylor WR, 2002. Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomized, multicentre trial. Lancet 359: 1365–1372.
Djimdé AA, Fofana B, Sagara I, Sidibe B, Toure S, Dembele D, Dama S, Ouologuem D, Dicko A, Doumbo OK, 2008. Efficacy, safety, and selection of molecular markers of drug resistance by two ACTs in Mali. Am J Trop Med Hyg 78: 455–461.
Dorsey G, Staedke S, Clark TD, Njama-Meya D, Nzarubara B, Maiteki-Sebuguzi C, Dokomajilar C, Kamya MR, Rosenthal PJ, 2007. Combination therapy for uncomplicated falciparum malaria in Ugandan children: a randomized trial. JAMA 297: 2210–2219.
Karema C, Fanello CI, van Overmeir C, van Geertruyden JP, van Doren W, Ngamije D, D'Alessandro U, 2006. Safety and efficacy of dihydroartemisinin/piperaquine (Artekin) for the treatment of uncomplicated Plasmodium falciparum malaria in Rwandan children. Trans R Soc Trop Med Hyg 100: 1105–1111.
Martensson A, Stromberg J, Sisowath C, Msellem MI, Gil JP, Montgomery SM, Olliaro P, Ali AS, Björkman A, 2005. Efficacy of artesunate plus amodiaquine versus that of artemether-lumefantrine for the treatment of uncomplicated childhood Plasmodium falciparum malaria in Zanzibar, Tanzania. Clin Infect Dis 41: 1079–1086.
Ndiaye JL, Randrianarivelojosia M, Sagara I, Brasseur P, Ndiaye I, Faye B, Randrianasolo L, Ratsimbasoa A, Forlemu D, Moor VA, Traore A, Niawanlou Dara YD, Lameyre V, Diallo M, Djimde A, Same-Ekobo A, Gaye O, 2009. Randomized, multicentre assessment of the efficacy and safety of ASAQ – a fixed-dose artesunate-amodiaquine combination therapy in the treatment of uncomplicated Plasmodium falciparum malaria. Malar J 8: 125.
Sirima SB, Tiono AB, Gansane A, Diarra A, Ouedraogo A, Konate AT, Kiechel JR, Morgan CC, Olliaro PL, Taylor WR, 2009. The efficacy and safety of a new fixed-dose combination of amodiaquine and artesunate in young African children with acute uncomplicated Plasmodium falciparum. Malar J 8: 48.
Zwang J, Olliaro P, Barennes H, Bonnet M, Brasseur P, Bukirwa H, Cohuet S, D'Alessandro U, Djimdé A, Karema C, Guthmann JP, Hamour S, Ndiaye JL, Mårtensson A, Rwagacondo C, Sagara I, Same-Ekobo A, Sirima SB, van den Broek I, Yeka A, Taylor WR, Dorsey G, Randrianarivelojosia M, 2009. Efficacy of artesunate-amodiaquine for treating uncomplicated falciparum malaria in sub-Saharan Africa: a multi-centre analysis. Malar J 8: 203.
Olliaro P, Djimdé A, Karema C, Mårtensson A, Ndiaye JL, Sirima SB, Dorsey G, Zwang J, 2011. Estimated versus actual parasitaemia in acute uncomplicated Plasmodium falciparum malaria in African children under five. Trop Med Int Health 16: 551–554.
Breusch TS, Pagan AR, 1980. The Lagrange multiplier test and its applications to model specification in econometrics. Rev Econ Stud 47: 239–253.
NIAID, 2007. Division of Microbiology and Infectious Diseases Pediatric Toxicity Tables. Available at: http://www.niaid.nih.gov. Accessed June 23, 2010.
McKenzie FE, Prudhomme WA, Magill AJ, Forney JR, Permpanich B, Lucas C, Gasser RA Jr, Wongsrichanalai C, 2005. White blood cell counts and malaria. J Infect Dis 192: 323–330.
Quintó L, Aponte JJ, Sacarlal J, Espasa M, Aide P, Mandomando I, Guinovart C, Macete E, Navia MM, Thompson R, Menéndez C, Alonso PL, 2006. Haematological and biochemical indices in young African children: in search of reference intervals. Trop Med Int Health 11: 1741–1748.
Jadhav UM, Singhvi R, Shah R, 2003. Prognostic implications of white cell differential count and white cell morphology in malaria. J Postgrad Med 49: 218–220.
Ladhani S, Lowe B, Cole AO, Kowuondo K, Newton CR, 2002. Changes in white blood cells and platelets in children with falciparum malaria: relationship to disease outcome. Br J Haematol 119: 839–847.
Sowunmi A, Akindele JA, Balogun MA, 1995. Leukocyte counts in falciparum malaria in African children from an endemic area. Afr J Med Sci 24: 145–149.
Gasasira AF, Kamya MR, Achan J, Mebrahtu T, Kalyango JN, Ruel T, Charlebois E, Staedke SG, Kekitiinwa A, Rosenthal PJ, Havlir D, Dorsey G, 2008. High risk of neutropenia in HIV-infected children following treatment with artesunate plus amodiaquine for uncomplicated malaria in Uganda. Clin Infect Dis 46: 985–991.
Dorsey G, Gasasira AF, Machekano R, Kamya MR, Staedke SG, Hubbard A, 2004. The impact of age, temperature, and parasite density on treatment outcomes from antimalarial clinical trials in Kampala, Uganda. Am J Trop Med Hyg 71: 531–536.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 58 | 58 | 10 |
Full Text Views | 358 | 119 | 2 |
PDF Downloads | 109 | 25 | 2 |