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| Name | Class |
|---|---|
| European Commission | OTHER |
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The overall objective is to evaluate the effect of exposure to Plasmodium (P.) falciparum erythrocytic stage antigens during different periods of infancy on the development of naturally acquired immunity (NAI).
Hypothesis: Exposure to P. falciparum prior to 5 months of age does not result in the development of NAI, while exposure to P. falciparum after 5 months of age leads to the development of NAI. The risks of clinical malaria and anaemia during the second year of life will be compared between cohorts, as well as their correlations with the type and quality of immune responses (antibodies to several P. falciparum antigens, cytokines), oxidative stress markers and host genetic factors. These results should shed light on the determinants of the development of anti-P. falciparum responses early in life and the potential constraints to early life immunisation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Late exposure group | Experimental | Participants received monthly Sulfadoxine-Pyrimethamine (SP) plus Artesunate (AS) from 2.5-4.5 months of age and monthly placebo from 5.5-9.5 months of age. |
|
| Early exposure group | Experimental | Participants received monthly placebo from 2.5-4.5 months of age and monthly SP+AS from 5.5-9.5 months of age. |
|
| Control group | Placebo Comparator | Participants received monthly placebo from 2.5 to 9.5 months of age. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sulfadoxine-pyrimethamine (SP) + Artesunate (AS) | Drug | Monthly chemoprophylaxis with SP (Fansidar® 500/25 mg) plus Artesunate (AS, Arsumax® 50 mg) or placebo (provided by Roche and Sanofi-Aventis) was administered according to the following age-based dosing schedule: ½ tablet of SP or placebo and ½ tablet of AS or placebo on the first day and ½ tablet of AS or placebo on the second and third days. |
| Measure | Description | Time Frame |
|---|---|---|
| (Clinical) Time to first or only episode of clinical malaria in the second year of life detected by passive case detection | Global comparison between the 3 groups of the time to first or only episode of clinical malaria (according to the primary case definition) in the second year of follow up detected by passive case detection in the According-To-Protocol cohort. In addition, pairwise comparisons of the 3 groups are also presented. | from 12 to 24 months of age |
| Measure | Description | Time Frame |
|---|---|---|
| (Clinical) Time to first or only episode of malaria (using other case definitions), anaemia and other clinical endpoints. | Global comparison between the 3 study groups of the time to first or only episode of clinical malaria (according to the secondary case definitions) in the second year of follow up detected by passive case detection. Other endpoints include multiple episodes of malaria, time to first or only episode of anaemia, total hospital visits and prevalence of parasitaemia and anaemia at different time points. In addition, pairwise comparisons of the 3 groups are also presented. |
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Inclusion Criteria:
Inclusion criteria for pregnant women:
Inclusion criteria for newborn infants:
Exclusion Criteria:
Exclusion criteria for pregnant women:
Exclusion criteria for newborn infants:
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| Name | Affiliation | Role |
|---|---|---|
| Pedro Alonso, MD, PhD | Barcelona Center for International Health Research, Hospital Clinic/University of Barcelona | Principal Investigator |
| Carlota Dobaño, PhD | Barcelona Center for International Health Research, Hospital Clinic/University of Barcelona | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centro de Investigaçao em Saude da Manhiça | Manhiça | Maputo Province | 1929 | Mozambique |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30380038 | Derived | Dobano C, Nhabomba AJ, Manaca MN, Berthoud T, Aguilar R, Quinto L, Barbosa A, Rodriguez MH, Jimenez A, Groves PL, Santano R, Bassat Q, Aponte JJ, Guinovart C, Doolan DL, Alonso PL. A Balanced Proinflammatory and Regulatory Cytokine Signature in Young African Children Is Associated With Lower Risk of Clinical Malaria. Clin Infect Dis. 2019 Aug 16;69(5):820-828. doi: 10.1093/cid/ciy934. | |
| 24674654 |
| Label | URL |
|---|---|
| CISM webpage | View source |
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| ID | Term |
|---|---|
| D008288 | Malaria |
| ID | Term |
|---|---|
| D011528 | Protozoan Infections |
| D010272 | Parasitic Diseases |
| D007239 | Infections |
| D000096724 | Mosquito-Borne Diseases |
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| ID | Term |
|---|---|
| C001205 | fanasil, pyrimethamine drug combination |
| D000077332 | Artesunate |
| ID | Term |
|---|---|
| D037621 | Artemisinins |
| D017382 | Reactive Oxygen Species |
| D005609 | Free Radicals |
| D007287 | Inorganic Chemicals |
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|
| 12 to 24 months of age |
| Oxidative stress markers | Quantification of the antioxidant/pro-oxidant status over the first two years of life in relation to age of first exposure to infection. | multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age) |
| Humoral and cellular immune responses | Quantification of antibody and cytokine responses to P. falciparum protein antigens and toxins over the first two years of life in relation to age of first exposure to infection | multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age) |
| Host genetics | Analysis of haematological genetic factors, polymorphisms in genes involved in inflammatory or immunological responses to malaria and polymorphisms in genes involved in the Th1/Th2 immunological pathway. | 2.5 months of age |
| Derived |
| Nhabomba AJ, Guinovart C, Jimenez A, Manaca MN, Quinto L, Cistero P, Aguilar R, Barbosa A, Rodriguez MH, Bassat Q, Aponte JJ, Mayor A, Chitnis CE, Alonso PL, Dobano C. Impact of age of first exposure to Plasmodium falciparum on antibody responses to malaria in children: a randomized, controlled trial in Mozambique. Malar J. 2014 Mar 27;13:121. doi: 10.1186/1475-2875-13-121. |
| 22412865 | Derived | Guinovart C, Dobano C, Bassat Q, Nhabomba A, Quinto L, Manaca MN, Aguilar R, Rodriguez MH, Barbosa A, Aponte JJ, Mayor AG, Renom M, Moraleda C, Roberts DJ, Schwarzer E, Le Souef PN, Schofield L, Chitnis CE, Doolan DL, Alonso PL. The role of age and exposure to Plasmodium falciparum in the rate of acquisition of naturally acquired immunity: a randomized controlled trial. PLoS One. 2012;7(3):e32362. doi: 10.1371/journal.pone.0032362. Epub 2012 Mar 7. |
| Barcelona Center for International Health Research | View source |
| D000079426 |
| Vector Borne Diseases |
| D009930 |
| Organic Chemicals |
| D012717 | Sesquiterpenes |
| D013729 | Terpenes |
| D006838 | Hydrocarbons |