Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to and : A Randomized Controlled Trial
Background:
Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria-related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv).
Methods and Findings:
In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10–43, p≤0.001) in children receiving SP-AQ and 12% (95% CI, −11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9–54, p = 0.012) and Pv incidence was 23% (95% CI, 0–41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4–51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, −24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p>0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%–2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention.
Conclusions:
IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv.
Trial registration:
ClinicalTrials.gov NCT00285662
: Please see later in the article for the Editors' Summary
Vyšlo v časopise:
Intermittent Preventive Treatment for Malaria in Papua New Guinean Infants Exposed to and : A Randomized Controlled Trial. PLoS Med 9(3): e32767. doi:10.1371/journal.pmed.1001195
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.1001195
Souhrn
Background:
Intermittent preventive treatment in infants (IPTi) has been shown in randomized trials to reduce malaria-related morbidity in African infants living in areas of high Plasmodium falciparum (Pf) transmission. It remains unclear whether IPTi is an appropriate prevention strategy in non-African settings or those co-endemic for P. vivax (Pv).
Methods and Findings:
In this study, 1,121 Papua New Guinean infants were enrolled into a three-arm placebo-controlled randomized trial and assigned to sulfadoxine-pyrimethamine (SP) (25 mg/kg and 1.25 mg/kg) plus amodiaquine (AQ) (10 mg/kg, 3 d, n = 374), SP plus artesunate (AS) (4 mg/kg, 3 d, n = 374), or placebo (n = 373), given at 3, 6, 9 and 12 mo. Both participants and study teams were blinded to treatment allocation. The primary end point was protective efficacy (PE) against all episodes of clinical malaria from 3 to 15 mo of age. Analysis was by modified intention to treat. The PE (compared to placebo) against clinical malaria episodes (caused by all species) was 29% (95% CI, 10–43, p≤0.001) in children receiving SP-AQ and 12% (95% CI, −11 to 30, p = 0.12) in those receiving SP-AS. Efficacy was higher against Pf than Pv. In the SP-AQ group, Pf incidence was 35% (95% CI, 9–54, p = 0.012) and Pv incidence was 23% (95% CI, 0–41, p = 0.048) lower than in the placebo group. IPTi with SP-AS protected only against Pf episodes (PE = 31%, 95% CI, 4–51, p = 0.027), not against Pv episodes (PE = 6%, 95% CI, −24 to 26, p = 0.759). Number of observed adverse events/serious adverse events did not differ between treatment arms (p>0.55). None of the serious adverse events were thought to be treatment-related, and the vomiting rate was low in both treatment groups (1.4%–2.0%). No rebound in malaria morbidity was observed for 6 mo following the intervention.
Conclusions:
IPTi using a long half-life drug combination is efficacious for the prevention of malaria and anemia in infants living in a region highly endemic for both Pf and Pv.
Trial registration:
ClinicalTrials.gov NCT00285662
: Please see later in the article for the Editors' Summary
Zdroje
1. World Health Organization 2010 Guidelines for the treatment of malaria Geneva World Health Organization
2. LengelerC 2004 Insecticide-treated bed nets and curtains for preventing malaria. Cochrane Database Syst Rev 2004 CD000363
3. PluessBTanserFCLengelerCSharpBL 2010 Indoor residual spraying for preventing malaria. Cochrane Database Syst Rev 2010 CD006657
4. SinclairDZaniBDoneganSOlliaroPGarnerP 2009 Artemisinin-based combination therapy for treating uncomplicated malaria. Cochrane Database Syst Rev 2009 CD007483
5. GreenwoodB 2004 The use of anti-malarial drugs to prevent malaria in the population of malaria-endemic areas. Am J Trop Med Hyg 70 1 7
6. GoslingRCairnsMChicoRChandramohanD 2010 May Intermittent preventive treatment against malaria: an update. Expert Rev Anti Infect Ther 8 589 606
7. MenendezCD'AlessandroUter KuileFO 2007 Reducing the burden of malaria in pregnancy by preventive strategies. Lancet Infect Dis 7 126 135
8. CrawleyJHillJYarteyJRobaloMSerufiliraA 2007 From evidence to action? Challenges to policy change and programme delivery for malaria in pregnancy. Lancet Infect Dis 7 145 155
9. GarnerPGülmezogluA 2006 Drugs for preventing malaria-related illness in pregnant women. Cochrane Database Syst Rev 2006 CD000169
10. AponteJSchellenbergDEganABreckenridgeACarneiroI 2009 Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials. Lancet 374 1533 1542
11. MeremikwuMMDoneganSEsuE 2008 Chemoprophylaxis and intermittent treatment for preventing malaria in children. Cochrane Database Syst Rev 2008 CD003756
12. Institute of Medicine of the National Academies 2008 Assessment of the role of intermittent preventive treatment for malaria in infants: letter report Washington (District of Columbia) Institute of Medicine of the National Academies
13. WilsonAL on behalf of the IPTc Taskforce 2011 A systematic review and meta-analysis of the efficacy and safety of intermittent preventive treatment of malaria in children (IPTc). PLoS ONE 6 e16976 doi:10.1371/journal.pone.0016976
14. GriffinJTCairnsMGhaniACRoperCSchellenbergD 2010 Protective efficacy of intermittent preventive treatment of malaria in infants (IPTi) using sulfadoxine-pyrimethamine and parasite resistance. PLoS ONE 5 e12618 doi:10.1371/journal.pone.0012618
15. MayorASerra-CasasESanzSAponteJJMaceteE 2008 Molecular markers of resistance to sulfadoxine-pyrimethamine during intermittent preventive treatment for malaria in Mozambican infants. J Infect Dis 197 1737 1742
16. GoslingRDGesaseSMoshaJFCarneiroIHashimR 2009 Protective efficacy and safety of three antimalarial regimens for intermittent preventive treatment for malaria in infants: a randomised, double-blind, placebo-controlled trial. Lancet 374 1521 1532
17. GesaseSGoslingRDHashimROrdRNaidooI 2009 High resistance of Plasmodium falciparum to sulphadoxine/pyrimethamine in northern Tanzania and the emergence of dhps resistance mutation at codon 581. PLoS ONE 4 e4569 doi:10.1371/journal.pone.0004569
18. World Health Organization 2010 WHO policy recommendation on intermittent preventive treatment during infancy with sulphadoxine-pyrimethamine (SP-IPTi) for Plasmodium falciparum malaria control in Africa Geneva World Health Organization
19. RosenbergR 2007 Plasmodium vivax in Africa: hidden in plain sight? Trends Parasitol 23 193 196
20. GentonBD'AcremontVRareLBaeaKReederJC 2008 Plasmodium vivax and mixed infections are associated with severe malaria in children: a prospective cohort study from Papua New Guinea. PLoS Med 5 e127 doi:10.1371/journal.pmed.0050127
21. LinEKiniboroBGrayLDobbieSRobinsonL 2010 Differential patterns of infection and disease with P. falciparum and P. vivax in young Papua New Guinean children. PLoS ONE 5 e9047 doi:10.1371/journal.pone.0009047
22. TjitraEAnsteyNMSugiartoPWarikarNKenangalemE 2008 Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia. PLoS Med 5 e128 doi:10.1371/journal.pmed.0050128
23. AlexandreMAFerreiraCOSiqueiraAMMagalhaesBLMouraoMP 2010 Severe Plasmodium vivax malaria, Brazilian Amazon. Emerg Infect Dis 16 1611 1614
24. LautzeJMcCartneyMKrishenPOlanaDJayasingheG 2007 Effect of a large dam on malaria risk: the Koka reservoir in Ethiopia. Trop Med Int Health 12 982 989
25. MuellerIGalinskiMRBairdJKCarltonJMKocharDK 2009 Key gaps in the knowledge of Plasmodium vivax, a neglected human malaria parasite. Lancet Infect Dis 9 555 566
26. HawkinsVNSuzukiSMRungsihirunratKHapuarachchiHCMaestreA 2009 Assessment of the origins and spread of putative resistance-conferring mutations in Plasmodium vivax dihydropteroate synthase. Am J Trop Med Hyg 81 348 355
27. CattaniJA 1992 The epidemiology of malaria in Papua New Guinea. AttenboroughRAlpersM Human biology in Papua New Guinea: the small cosmos Oxford Clarendon Press 302 312
28. SchultzLWaplingJMuellerINtsukePOSennN 2010 Multilocus haplotypes reveal variable levels of diversity and population structure of Plasmodium falciparum in Papua New Guinea, a region of intense perennial transmission. Malar J 9 336
29. SchellenbergDCisseBMenendezC 2006 The IPTi Consortium: research for policy and action. Trends Parasitol 22 296 300
30. ReedRBSuartHC 1959 Patterns of growth in height and weight from birth to eighteen years of age. Pediatrics 24 904 921
31. McNamaraDTThomsonJMKasehagenLJZimmermanPA 2004 Development of a multiplex PCR-ligase detection reaction assay for diagnosis of infection by four human malaria parasite species. J Clin Microbol 42 2403 2410
32. KasehagenLJMuellerIMcNamaraDTBockarieMJKiniboroB 2006 Changing patterns of Plasmodium blood-stage infections in the Wosera region of Papua New Guinea monitored by light microscopy and high throughput PCR diagnosis. Am J Trop Med Hyg 75 588 596
33. MullerIGentonBRareLKiniboroBKastensW 2009 Three different Plasmodium species show similar patterns of clinical tolerance of malaria infection. Malar J 8 158
34. OdhiamboFOHamelMJWilliamsonJLindbladeKter KuileFO 2010 Intermittent preventive treatment in infants for the prevention of malaria in rural western Kenya: a randomized, double-blind placebo-controlled trial. PLoS ONE 5 e10016 doi:10.1371/journal.pone.0010016
35. MayJAdjeiSBuschWGaborJIssifouS 2008 Therapeutic and prophylactic effect of intermittent preventive anti-malarial treatment in infants (IPTi) from Ghana and Gabon. Malar J 7 198
36. KrotoskiWA 1989 The hypnozoite and malarial relapse. Prog Clin Parasitol 1 1 19
37. CraigeBAlvingASJonesRMerrill WhortonCPullmanTN 1947 The Chesson strain of Plasmodium vivax malaria: II. Relationship between prepatent period, latent period and relapse rate. J Infect Dis 80 228 236
38. KarunajeewaHAMuellerISennMLinELawI 2008 A trial of combination antimalarial therapies in children from Papua New Guinea. N Engl J Med 359 2545 2557
39. MarfurtJMuellerISieAMakuPGorotiM 2007 Low efficacy of amodiaquine or chloroquine plus sulfadoxine-pyrimethamine against Plasmodium falciparum and P. vivax malaria in Papua New Guinea. Am J Trop Med Hyg 77 947 954
40. KoepfliCMuellerIMarfurtJGorotiMSieA 2009 Evaluation of Plasmodium vivax genotyping markers for molecular monitoring in clinical trials. J Infect Dis 199 1074 1080
41. BarnadasCKoepfliCKarunajeewaHASibaPMDavisTME 2011 Characterization of treatment failure in efficacy trials of drugs against Plasmodium vivax by genotyping neutral and drug resistance-associated markers. Antimicrob Agents Chemother 55 4479 4481
42. PicotSOlliaroPde MonbrisonFBienvenuAPriceRN 2009 A systematic review and meta-analysis of evidence for correlation between molecular markers of parasite resistance and treatment outcome in falciparum malaria. Malaria J 8 89
43. MarfurtJde MonbrisonFBregaSBarbollatLMullerI 2008 Molecular markers of in vivo Plasmodium vivax resistance to amodiaquine plus sulfadoxine-pyrimethamine: mutations in pvdhfr and pvmdr1. J Infect Dis 198 409 417
44. HawkinsVNJoshiHRungsihirunratKNa-BangchangKSibleyCH 2007 Antifolates can have a role in the treatment of Plasmodium vivax. Trends Parasitol 23 213 222
45. WongRPKarunajeewaHMuellerISibaPZimmermanPA 2011 Molecular assessment of Plasmodium falciparum resistance to antimalarial drugs in Papua New Guinea using an extended ligase detection reaction fluorescent microsphere assay. Antimicrob Agents Chemother 55 798 805
46. RieckmannKHDavisDRHuttonDC 1989 Plasmodium vivax resistance to chloroquine? Lancet 2 1183 1184
47. MullerIBockarieMAlpersMSmithT 2003 The epidemiology of malaria in Papua New Guinea. Trends Parasitol 19 253 259
48. MehlotraRKFujiokaHRoepePDJannehOUrsosLM 2001 Evolution of a unique Plasmodium falciparum chloroquine-resistance phenotype in association with pfcrt polymorphism in Papua New Guinea and South America. Proc Natl Acad Sci U S A 98 12689 12694
49. KarunajeewaHAIlettKFDufallKKemikiABockarieM 2004 Disposition of artesunate and dihydroartemisinin after administration of artesunate suppositories in children from Papua New Guinea with uncomplicated malaria. Antimicrob Agents Chemother 48 2966 2972
50. SalmanSKoseKGriffinSBaiwogFWinmaiJ 2011 The pharmacokinetic properties of standard and double-dose sulfadoxine-pyrimethamine in infants. Antimicrob Agents Chemother 55 1693 1700
51. StepniewskaKTaylorWSirimaSBOuedraogoEBOuedraogoA 2009 Population pharmacokinetics of artesunate and amodiaquine in African children. Malar J 8 200
52. WhiteNJ 2005 Intermittent presumptive treatment for malaria. PLoS Med 2 e3 doi:10.1371/journal.pmed.0020003
53. Armstrong SchellenbergJRMShirimaKMaokolaWManziFMrishoM 2010 Community effectiveness of intermittent preventive treatment for infants (IPTi) in rural southern Tanzania. Am J Trop Med Hyg 82 772 781
54. MwesigwaJParikhSMcGeeBGermanPDrysdaleT 2010 Pharmacokinetics of artemether-lumefantrine and artesunate-amodiaquine in children in Kampala, Uganda. Antimicrob Agents Chemother 54 52 59
55. PellCStrausLPhuanukoonnonSLupiwaSMuellerI 2010 Community response to intermittent preventive treatment of malaria in infants (IPTi) in Papua New Guinea. Malar J 9 369
56. RossAMaireNSicuriESmithTContehL 2011 Determinants of the cost-effectiveness of intermittent preventive treatment for malaria in infants and children. PLoS ONE 6 e18391 doi:10.1371/journal.pone.0018391
57. ContehLSicuriEManziFHuttonGObonyoB 2010 The cost-effectiveness of intermittent preventive treatment for malaria in infants in sub-Saharan Africa. PLoS ONE 5 e10313 doi:10.1371/journal.pone.0010313
Štítky
Interné lekárstvoČlánok vyšiel v časopise
PLOS Medicine
2012 Číslo 3
- MUDr. Dana Vondráčková: Hepatopatie sú pri liečbe metamizolom väčším strašiakom ako agranulocytóza
- Metamizol v liečbe pooperačnej bolesti u detí do 6 rokov veku
- Parazitičtí červi v terapii Crohnovy choroby a dalších zánětlivých autoimunitních onemocnění
- Vztah mezi statiny a rizikem vzniku nádorových onemocnění − metaanalýza
- Statiny indukovaná myopatie: Jak na diferenciální diagnostiku?
Najčítanejšie v tomto čísle
- Guidance for Evidence-Informed Policies about Health Systems: Assessing How Much Confidence to Place in the Research Evidence
- Uterine Rupture by Intended Mode of Delivery in the UK: A National Case-Control Study
- Guidance for Evidence-Informed Policies about Health Systems: Linking Guidance Development to Policy Development
- Improving Ethical Review of Research Involving Incentives for Health Promotion