Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria : a literature review and meta-analysis of individual patient data
WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England.
D'Alessandro, Umberto (författare)
Inst Trop Med, Unit Malariol, B-2000 Antwerp, Belgium.;MRC Unit, Fajara, Gambia.;London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Dis Control, London WC1, England.
Desai, Meghna (författare)
Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Malaria Branch, Atlanta, GA USA.
Dicko, Alassane (författare)
Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali.;Univ Bamako, Fac Med Pharm & Dent, Dept Publ Hlth, Bamako, Mali.
Djimde, Abdoulaye A. (författare)
Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali.
Dorsey, Grant (författare)
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
Doumbo, Ogobara K. (författare)
Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali.
Drakeley, Chris J. (författare)
German Ctr Infect Res, Tubingen, Germany.
Duparc, Stephan (författare)
Med Malaria Venture, Geneva, Switzerland.
Eshetu, Teferi (författare)
Univ Barcelona, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Hosp Clin, Barcelona, Spain.;Jimma Univ, Dept Med Lab Sci & Pathol, Jimma, Ethiopia.
Espie, Emmanuelle (författare)
Epictr, Paris, France.
Etard, Jean-Francois (författare)
Epictr, Paris, France.;IRD, Montpellier, France.
Faiz, Abul M. (författare)
Mahidol Univ, Fac Trop Med, Bangkok, Thailand.
Falade, Catherine O. (författare)
Univ Ibadan, Coll Med, Dept Pharmacol & Therapeut, Ibadan, Nigeria.
Fanello, Caterina I. (författare)
Mahidol Univ, Fac Trop Med, Mahidol Oxford Res Unit, Bangkok, Thailand.
Faucher, Jean-Francois (författare)
IRD, Mother & Child Hlth Trop Res Unit, Paris, France.;Univ Paris 05, PRES Sorbonne Paris Cite, Paris, France.;Univ Besancon, Med Ctr, Dept Infect Dis, F-25030 Besancon, France.
Karolinska Inst, Pharmacogenet Sect, Drug Resistance Unit, Dept Physiol & Pharmacol, Stockholm, Sweden.;Univ Lisbon, Fac Sci, Biosyst & Integrat Sci Inst BioISI, P-1699 Lisbon, Portugal.;SUNY Binghamton, Harpur Coll Arts & Sci, Binghamton, NY USA.
Gonzalez, Raquel (författare)
Ctr Invest Saude Manhica, Manhica, Mozambique.;Univ Barcelona, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Hosp Clin, Barcelona, Spain.
Grandesso, Francesco (författare)
Epictr, Paris, France.
Greenhouse, Bryan (författare)
Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
Greenwood, Brian (författare)
London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Dis Control, London WC1, England.
Grivoyannis, Anastasia (författare)
Univ Washington, Div Emergency Med, Seattle, WA 98195 USA.
Guerin, Philippe J. (författare)
WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England.
Guthmann, Jean-Paul (författare)
Inst Veille Sanit, Dept Malad Infect, St Maurice, France.
Hamed, Kamal (författare)
Novartis Pharmaceut, E Hanover, NJ USA.
Hamour, Sally (författare)
Royal Free Hosp, UCL Ctr Nephrol, London NW3 2QG, England.
Hay, Simon I. (författare)
Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.;Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.;NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
WorldWide Antimalarial Resistance Network WWARN, Oxford, England.;Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England.
Hwang, Jimee (författare)
Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Malaria Branch, Atlanta, GA USA.;Univ Calif San Francisco, Global Hlth Grp, San Francisco, CA 94143 USA.
Ibrahim, Maman L. (författare)
Ctr Rech Med & Sanit, Niamey, Niger.
Jima, Daddi (författare)
Fed Minist Hlth, Addis Ababa, Ethiopia.
Jones, Joel J. (författare)
Minist Hlth & Social Welf, Natl Malaria Control Programme, Monrovia, Liberia.
Jullien, Vincent (författare)
Univ Paris 05, AP HP, Paris, France.
Juma, Elizabeth (författare)
Kenya Govt Med Res Ctr, Nairobi, Kenya.
Kachur, Patrick S. (författare)
Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Malaria Branch, Atlanta, GA USA.
Kager, Piet A. (författare)
Univ Amsterdam, Acad Med Ctr, Ctr Infect & Immun Amsterdam CINIMA, Div Infect Dis Trop Med & AIDS, NL-1105 AZ Amsterdam, Netherlands.
Kamugisha, Erasmus (författare)
Catholic Univ Hlth & Allied Sci, Mwanza, Tanzania.
Kamya, Moses R. (författare)
Makerere Univ, Coll Hlth Sci, Kampala, Uganda.
Karema, Corine (författare)
Minist Hlth, Malaria & Other Parasit Dis Div RBC, Kigali, Rwanda.
Kayentao, Kassoum (författare)
Univ Bamako, Fac Med Pharm & Dent, Malaria Res & Training Ctr, Bamako, Mali.
Muhimbili Univ Hlth & Allied Sci, Dept Parasitol, Dar Es Salaam, Tanzania.;Karolinska Inst, Dept Med Solna, Infect Dis Unit, Malaria Res, Stockholm, Sweden.
London Sch Hyg & Trop Med, Fac Infect & Trop Dis, Dept Infect & Immun, London WC1, England.
Ogutu, Bernhards R. (författare)
United States Army Med Res Unit, Kenya Med Res Inst, Kisumu, Kenya.
Olliaro, Piero (författare)
Univ Oxford, Nuffield Dept Clin Med, Ctr Trop Med & Global Hlth, Oxford, England.;UNICEF UNDP World Bank WHO Special Programme Res, Geneva, Switzerland.
Omar, Sabah A. (författare)
Kenya Govt Med Res Ctr, Ctr Biotechnol Res & Dev, Nairobi, Kenya.
East Africa Reg Ctr, WorldWide Antimalarial Resistance Network WWARN, Nairobi, Kenya.;Univ Oxford, KEMRI, Wellcome Trust Res Programme, Nairobi, Kenya.
Taylor, Walter R. J. (författare)
UNICEF UNDP World Bank WHO Special Programme Res, Geneva, Switzerland.;Hop Cantonal Univ Geneva, Serv Med Int & Humanitaire, Geneva, Switzerland.
Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs). Methods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials (uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa, between 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial Resistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological response were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in included studies was evaluated based on study design, methodology and missing data. Results: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine (n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite clearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5-64.9) on day 1 to 6.7 % (95 % CI: 4.8-8.7) on day 2 and 0.9 % (95 % CI: 0.5-1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %. Independent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16 (95 % CI: 1.08-1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 degrees C) (AOR = 1.50 (95 % CI: 1.06-2.13), P = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21-3.44), P = 0.008); areas of low/moderate transmission setting (AOR = 2.71 (95 % CI: 1.38-5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine (AOR = 2.27 (95 % CI: 1.14-4.51), P = 0.020, compared to dihydroartemisinin-piperaquine). Conclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across the sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50 patients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold of 10 % to trigger further investigation of artemisinin susceptibility.
Ämnesord
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Infectious Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Infektionsmedicin (hsv//swe)
MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)