Intermittent Preventive Treatment of Malaria Provides Substantial Protection against Malaria in Children Already Protected by an Insecticide-Treated Bednet in Mali: A Randomised, Double-Blind, Placebo-Controlled Trial
Background:
Previous studies have shown that in areas of seasonal malaria transmission, intermittent preventive treatment of malaria in children (IPTc), targeting the transmission season, reduces the incidence of clinical malaria. However, these studies were conducted in communities with low coverage with insecticide-treated nets (ITNs). Whether IPTc provides additional protection to children sleeping under an ITN has not been established.
Methods and Findings:
To assess whether IPTc provides additional protection to children sleeping under an ITN, we conducted a randomised, double-blind, placebo-controlled trial of IPTc with sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) in three localities in Kati, Mali. After screening, eligible children aged 3–59 mo were given a long-lasting insecticide-treated net (LLIN) and randomised to receive three rounds of active drugs or placebos. Treatments were administered under observation at monthly intervals during the high malaria transmission season in August, September, and October 2008. Adverse events were monitored immediately after the administration of each course of IPTc and throughout the follow-up period. The primary endpoint was clinical episodes of malaria recorded through passive surveillance by study clinicians available at all times during the follow-up. Cross-sectional surveys were conducted in 150 randomly selected children weekly and in all children at the end of the malaria transmission season to assess usage of ITNs and the impact of IPTc on the prevalence of malaria, anaemia, and malnutrition. Cox regression was used to compare incidence rates between intervention and control arms. The effects of IPTc on the prevalence of malaria infection and anaemia were estimated using logistic regression. 3,065 children were screened and 3,017 (1,508 in the control and 1,509 in the intervention arm) were enrolled in the study. 1,485 children (98.5%) in the control arm and 1,481 (98.1%) in the intervention arm completed follow-up. During the intervention period, the proportion of children reported to have slept under an ITN was 99.7% in the control and 99.3% in intervention arm (p = 0.45). A total of 672 episodes of clinical malaria defined as fever or a history of fever and the presence of at least 5,000 asexual forms of Plasmodium falciparum per microlitre (incidence rate of 1.90; 95% confidence interval [CI] 1.76–2.05 episodes per person year) were observed in the control arm versus 126 (incidence rate of 0.34; 95% CI 0.29–0.41 episodes per person year) in the intervention arm, indicating a protective effect (PE) of 82% (95% CI 78%–85%) (p<0.001) on the primary endpoint. There were 15 episodes of severe malaria in children in the control arm compared to two in children in the intervention group giving a PE of 87% (95% CI 42%–99%) (p = 0.001). IPTc reduced the prevalence of malaria infection by 85% (95% CI 73%–92%) (p<0.001) during the intervention period and by 46% (95% CI 31%–68%) (p<0.001) at the end of the intervention period. The prevalence of moderate anaemia (haemoglobin [Hb] <8 g/dl) was reduced by 47% (95% CI 15%–67%) (p<0.007) at the end of intervention period. The frequencies of adverse events were similar between the two arms. There was no drug-related serious adverse event.
Conclusions:
IPTc given during the malaria transmission season provided substantial protection against clinical episodes of malaria, malaria infection, and anaemia in children using an LLIN. SP+AQ was safe and well tolerated. These findings indicate that IPTc could make a valuable contribution to malaria control in areas of seasonal malaria transmission alongside other interventions.
Trial Registration: ClinicalTrials.gov NCT00738946
: Please see later in the article for the Editors' Summary
Vyšlo v časopise:
Intermittent Preventive Treatment of Malaria Provides Substantial Protection against Malaria in Children Already Protected by an Insecticide-Treated Bednet in Mali: A Randomised, Double-Blind, Placebo-Controlled Trial. PLoS Med 8(2): e32767. doi:10.1371/journal.pmed.1000407
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pmed.1000407
Souhrn
Background:
Previous studies have shown that in areas of seasonal malaria transmission, intermittent preventive treatment of malaria in children (IPTc), targeting the transmission season, reduces the incidence of clinical malaria. However, these studies were conducted in communities with low coverage with insecticide-treated nets (ITNs). Whether IPTc provides additional protection to children sleeping under an ITN has not been established.
Methods and Findings:
To assess whether IPTc provides additional protection to children sleeping under an ITN, we conducted a randomised, double-blind, placebo-controlled trial of IPTc with sulphadoxine pyrimethamine (SP) plus amodiaquine (AQ) in three localities in Kati, Mali. After screening, eligible children aged 3–59 mo were given a long-lasting insecticide-treated net (LLIN) and randomised to receive three rounds of active drugs or placebos. Treatments were administered under observation at monthly intervals during the high malaria transmission season in August, September, and October 2008. Adverse events were monitored immediately after the administration of each course of IPTc and throughout the follow-up period. The primary endpoint was clinical episodes of malaria recorded through passive surveillance by study clinicians available at all times during the follow-up. Cross-sectional surveys were conducted in 150 randomly selected children weekly and in all children at the end of the malaria transmission season to assess usage of ITNs and the impact of IPTc on the prevalence of malaria, anaemia, and malnutrition. Cox regression was used to compare incidence rates between intervention and control arms. The effects of IPTc on the prevalence of malaria infection and anaemia were estimated using logistic regression. 3,065 children were screened and 3,017 (1,508 in the control and 1,509 in the intervention arm) were enrolled in the study. 1,485 children (98.5%) in the control arm and 1,481 (98.1%) in the intervention arm completed follow-up. During the intervention period, the proportion of children reported to have slept under an ITN was 99.7% in the control and 99.3% in intervention arm (p = 0.45). A total of 672 episodes of clinical malaria defined as fever or a history of fever and the presence of at least 5,000 asexual forms of Plasmodium falciparum per microlitre (incidence rate of 1.90; 95% confidence interval [CI] 1.76–2.05 episodes per person year) were observed in the control arm versus 126 (incidence rate of 0.34; 95% CI 0.29–0.41 episodes per person year) in the intervention arm, indicating a protective effect (PE) of 82% (95% CI 78%–85%) (p<0.001) on the primary endpoint. There were 15 episodes of severe malaria in children in the control arm compared to two in children in the intervention group giving a PE of 87% (95% CI 42%–99%) (p = 0.001). IPTc reduced the prevalence of malaria infection by 85% (95% CI 73%–92%) (p<0.001) during the intervention period and by 46% (95% CI 31%–68%) (p<0.001) at the end of the intervention period. The prevalence of moderate anaemia (haemoglobin [Hb] <8 g/dl) was reduced by 47% (95% CI 15%–67%) (p<0.007) at the end of intervention period. The frequencies of adverse events were similar between the two arms. There was no drug-related serious adverse event.
Conclusions:
IPTc given during the malaria transmission season provided substantial protection against clinical episodes of malaria, malaria infection, and anaemia in children using an LLIN. SP+AQ was safe and well tolerated. These findings indicate that IPTc could make a valuable contribution to malaria control in areas of seasonal malaria transmission alongside other interventions.
Trial Registration: ClinicalTrials.gov NCT00738946
: Please see later in the article for the Editors' Summary
Zdroje
1. United Nations 2008 World population prospects. The 2008 revision volume ii: sex and age distribution of the world population. Available: http://esa.un.org/unpd/wpp2008/peps_documents.htm Accessed 21 November 2010
2. WHO 2008 World malaria report, 2008. Available: http://www.who.int/malaria/wmr2008/malaria2008.pdf Accessed 10 May 2010
3. LengelerC
2004 Insecticide-treated bed nets and curtains for preventing malaria. Cochrane Database Syst Rev CD000363
4. AponteJJ
SchellenbergD
EganA
BreckenridgeA
CarneiroI
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
5. TaylorT
OlolaC
ValimC
AgbenyegaT
KremsnerP
2006 Standardized data collection for multi-center clinical studies of severe malaria in African children: establishing the SMAC network. Trans R Soc Trop Med Hyg 100 615 622
6. DickoA
SagaraI
SissokoMS
GuindoO
DialloAI
2008 Impact of intermittent preventive treatment with sulphadoxine-pyrimethamine targeting the transmission season on the incidence of clinical malaria in children in Mali. Malar J 7 123
7. CisséB
SokhnaC
BoulangerD
MiletJ
Bâ elH
2006 Seasonal intermittent preventive treatment with artesunate and sulfadoxine-pyrimethamine for prevention of malaria in Senegalese children: a randomised, placebo-controlled, double-blind trial. Lancet 367 659 667
8. SokhnaC
CisséB
Bâ elH
MilliganP
HallettR
2008 A trial of the efficacy, safety and impact on drug resistance of four drug regimens for seasonal intermittent preventive treatment for malaria in Senegalese children. PLoS One 3 e1471 doi:10.1371/journal.pone.0001471
9. KwekuM
LiuD
AdjuikM
BinkaF
SeiduM
2008 Seasonal intermittent preventive treatment for the prevention of anaemia and malaria in Ghanaian children: a randomized, placebo controlled trial. PLoS One 3 e4000 doi:10.1371/journal.pone.0004000
10. SteketeeRW
EiseleTP
2009 Is the scale up of malaria intervention coverage also achieving equity? PLoS One 4 e8409 doi:10.1371/journal.pone.0008409
11. Roll Back Malaria. Global malaria action plan for a malaria free world. Available: http://www.rollbackmalaria.org/gmap/gmap.pdf Accessed 10 May 2010
12. World Health Organization 2000 Severe falciparum malaria. Trans R Soc Trop Med Hyg 94 S1 S90
13. WHO 2006 Child growth standards. Available: http://www.who.int/childgrowth/standards/chart_catalogue/en/index.html Accessed 10 May 2010
14. PloweCV
DjimdeA
BouareM
DoumboO
WellemsTE
1995 Pyrimethamine and proguanil resistance-conferring mutations in Plasmodium falciparum dihydrofolate reductase: polymerase chain reaction methods for surveillance in Africa. Am J Trop Med Hyg 52 565 568
15. DjimdéA
DoumboOK
CorteseJF
KayentaoK
DoumboS
2001 A molecular marker for chloroquine-resistant falciparum malaria. N Engl J Med 344 257 263
16. DickoA
SagaraI
DjimdéAA
TouréSO
TraoreM
2010 Molecular markers of resistance to sulphadoxine-pyrimethamine one year after implementation of intermittent preventive treatment of malaria in infants in Mali. Malar J 9 9
17. SmithPG
MorrowR
1996 Field trials of health interventions in developing countries: a toolbox. London Macmillan
18. MbayeA
RichardsonK
BalajoB
DunyoS
ShulmanC
2006 A randomized, placebo-controlled trial of intermittent preventive treatment with sulphadoxine-pyrimethamine in Gambian multigravidae. Trop Med Int Health 11 992 1002
19. MenéndezC
BardajíA
SigauqueB
RomagosaC
SanzS
2008 A randomized placebo-controlled trial of intermittent preventive treatment in pregnant women in the context of insecticide treated nets delivered through the antenatal clinic. PLoS One 3 e1934 doi:10.1371/journal.pone.0001934
20. SagaraI
SangaréD
DoloG
GuindoA
SissokoM
2002 A high malaria reinfection rate in children and young adults living under a low entomological inoculation rate in a periurban area of Bamako, Mali. Am J Trop Med Hyg 66 310 313
21. DickoA
SagaraI
DiemertD
SogobaM
NiambeleMB
2007 Year-to-year variation in the age-specific incidence of clinical malaria in two potential vaccine testing sites in Mali with different levels of malaria transmission intensity. Am J Trop Med Hyg 77 1028 1033
22. SirimaSB
KonatéA
TionoAB
ConvelboN
Cousens, et al. 2003 Early treatment of childhood fevers with pre-packaged antimalarial drugs in the home reduces severe malaria morbidity in Burkina Faso. Trop Med Int Health 8 133 139
23. KidaneG
MorrowRH
2000 Teaching mothers to provide home treatment of malaria in Tigray, Ethiopia: a randomised trial. Lancet 356 550 555
24. CairnsM
GoslingR
CarneiroI
GesaseS
MoshaJF
2010 Duration of protection against clinical malaria provided by three regimens of intermittent preventive treatment in Tanzanian infants. PLoS One 5 e9467 doi:10.1371/journal.pone.0009467
25. NtabB
CisséB
BoulangerD
SokhnaC
TargettG
2007 Impact of intermittent preventive anti-malarial treatment on the growth and nutritional status of preschool children in rural Senegal (west Africa). Am J Trop Med Hyg 77 411 417
26. KonatéAT
YaroJB
OuédraogoAZ
DiarraA
GansanéA
Intermittent preventive treatment of malaria provides substantial protection against malaria in children already protected by an insecticide treated bednet in Burkina Faso. PLoS Med 8 e1000408 doi:10.1371/journal.pmed.1000408
27. GreenwoodB
2006 Review: intermittent preventive treatment–a new approach to the prevention of malaria in children in areas with seasonal malaria transmission. Trop Med Int Health 11 983 991
28. Report of the Technical Expert Group (TEG) Meeting on Intermittent Preventive Therapy in Infancy (IPTi) 2007 Geneva, 8–10 October 2007. Available: http://malaria.who.int/docs/IPTi/TEGConsultIPTiOct2007Report.pdf. Accessed 10 May 2010
29. BuffetPA
BriandV
RéniaL
ThellierM
DanisM
2008 Intermittent preventive antimalarial treatment to children (IPTc): firebreak or fire trap? Trends Parasitol 24 482 485
30. KwekuM
WebsterJ
AdjuikM
AbudeyS
GreenwoodB
2009 Options for the delivery of intermittent preventive treatment for malaria to children: a community randomised trial. PLoS One 4 e7256 doi:10.1371/journal.pone.0007256
31. CairnsM
GoslingR
GesaseS
MoshaJ
GreenwoodB
2009 Mode of action and choice of antimalarial drugs for intermittent preventive treatment in infants. Trans R Soc Trop Med Hyg 103 1199 1201
32. CairnsM
CarneiroI
MilliganP
Owusu-AgyeiS
AwineT
2008 Duration of protection against malaria and anaemia provided by intermittent preventive treatment in infants in Navrongo, Ghana. PLoS One 3 e2227 doi:10.1371/journal.pone.0002227
33. BojangKA
AkorF
ContehL
WebbEL
BittayeO
Two strategies for the delivery of IPTc in an area of seasonal malaria transmission in The Gambia: a randomised controlled trial. PLoS Med 8 e1000409 doi:10.1371/journal.pmed.1000409
34. DickoA
BarryM
DickoM
SagaraI
RogierC
2010 Morbidité palustre en fonction de l'âge et de la saison à Nossoumbougou dans le cercle de Kolokani au Mali. Rev Epidemiol Sante Publique 58 S90 S91
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