effect of 4 years of seasonal malaria chemoprevention on the acquisition of antibodies CORD-Papers-2022-06-02 (Version 1)

Title: Effect of 4 years of seasonal malaria chemoprevention on the acquisition of antibodies to Plasmodium falciparum antigens in Ouelessebougou Mali
Abstract: BACKGROUND: More than 200 million people live in areas of highly seasonal malaria transmission where Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) was recommended in 2012 by WHO. This strategy is now implemented widely and protected more than 19 million children in 2018. It was previously reported that exposure to SMC reduced antibody levels to AMA1 MSP-1(42) and CSP but the duration of exposure to SMC up to three 3 years had no effect on antibody levels to MSP-1(42) and CSP. METHODS: In 2017 a cross-sectional survey was carried out 1 month after the last dose of SMC had been given to children aged 45 years randomly selected from areas where SMC had been given for 2 or 4 years during the malaria transmission season. A total of 461 children were enrolled 242 children in areas where SMC had been implemented for 4 years and 219 children in areas where SMC had been implemented for 2 years. Antibody extracted from dry blood spots was used to measure IgG levels to the malaria antigens CSP MSP-1(42) and AMA1 by ELISA. RESULTS: The prevalence of antibodies to MSP-1(42) was similar in children who had received SMC for 4 years compared to those who had received SMC for only 2 years (85.1 vs 86.0% ajusted odd ratio (aOR) = 1.06 95% confidence intervals (CI 0.621.80) p = 0.80). The prevalence of antibodies to AMA-1 and to CSP was not lower in children who received SMC for 4 years compared to those who had received SMC for only 2 years (95.3 vs 88.8% aOR = 3.16 95% CI 1.446.95 p = 0.004 for AMA-1; and 91.2 vs 81.9% aOR = 3.14 95% CI 1.705.76 p < 0.001 for CSP). Median antibody levels for anti-MSP-1(42) IgG were not significatively inferior in children who had received SMC for four rather than 2 years (0.88 (IQR: 0.641.15) and 0.95 ((0.681.15) respectively) anti-CSP (1.30 (1.001.56) and 1.17 (0.871.47)) and anti-AMA-1 (1.45 (1.241.68) and 1.41 (1.171.64)). CONCLUSION: In an area of high seasonal malaria transmission children who had received SMC for 4 years did not had lower seropositivity or antibody levels to AMA1 MSP-1(42) and CSP compared to children who had received SMC for only 2 years suggesting that children who have received SMC for 4 years may not be more at risk of malaria after the cessation of SMC than children who have received SMC for a shorter period.
Published: 2021-01-07
Journal: Malar J
DOI: 10.1186/s12936-020-03542-9
DOI_URL: http://doi.org/10.1186/s12936-020-03542-9
Author Name: Mahamar Almahamoudou
Author link: https://covid19-data.nist.gov/pid/rest/local/author/mahamar_almahamoudou
Author Name: Issiaka Djibrilla
Author link: https://covid19-data.nist.gov/pid/rest/local/author/issiaka_djibrilla
Author Name: Youssouf Ahamadou
Author link: https://covid19-data.nist.gov/pid/rest/local/author/youssouf_ahamadou
Author Name: Niambele Sidi M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/niambele_sidi_m
Author Name: Soumare Harouna M
Author link: https://covid19-data.nist.gov/pid/rest/local/author/soumare_harouna_m
Author Name: Attaher Oumar
Author link: https://covid19-data.nist.gov/pid/rest/local/author/attaher_oumar
Author Name: Barry Amadou
Author link: https://covid19-data.nist.gov/pid/rest/local/author/barry_amadou
Author Name: Narum David L
Author link: https://covid19-data.nist.gov/pid/rest/local/author/narum_david_l
Author Name: Duffy Patrick E
Author link: https://covid19-data.nist.gov/pid/rest/local/author/duffy_patrick_e
Author Name: Greenwood Brian
Author link: https://covid19-data.nist.gov/pid/rest/local/author/greenwood_brian
Author Name: Fried Michal
Author link: https://covid19-data.nist.gov/pid/rest/local/author/fried_michal
Author Name: Dicko Alassane
Author link: https://covid19-data.nist.gov/pid/rest/local/author/dicko_alassane
sha: 07523b17a4758fef4cd2c2fdc06a2b00686affbb
license: cc-by
license_url: https://creativecommons.org/licenses/by/4.0/
source_x: PMC
source_x_url: https://www.ncbi.nlm.nih.gov/pubmed/
pmcid: PMC7788529
pmcid_url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788529
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788529/
has_full_text: TRUE
Keywords Extracted from Text Content: IgG amodiaquine people children AQ line SMC blood Author(s anti-CSP AMA-1 sulfadoxine-pyrimethamine MSP-1 42 AMA1 Immunoglobulin G MSP-1 19 Mali GLURP antigen blood cells clone AQ Plasmodium falciparum erythrocytic-stage antigens [1] SIGMA FAST Ouelessebougou MSP-1 ODs dapsone High-binding 96-well Senegal [18] TNF MSP-1 42 blood samples AMA1 Anti-MSP-1 Anti-CSP amodiaquine children P. falciparum antigens Fig. 1 − pyrimethamine children 3-59 serum P. falciparum dihydroartemisininpiperaquine [8 WBCs AMA-1 sulfadoxine-pyrimethamine AMA1) antigens microscopist HBX4 WBC/μL. hyperimmune serum Senegal [7 anti-malarials Anti-AMA1 Pichia pastoris IL-2 recombinant P. falciparum 3D7 Africa's Sahel Escherichia coli [13 tablet IgG antibodies azithromycin recombinant AMA-1 CD4 phosphate buffered saline dihydroartemisinin-piperaquine IgG IL-10/ Niger [9 SMC blood Burkina Faso [4 Gambia plasmodial antigens saponin Tween sera TNF-α malaria-naïve SP + AQ 250/12.5 red blood cells participants parents/guardians
Extracted Text Content in Record: First 5000 Characters:Background: More than 200 million people live in areas of highly seasonal malaria transmission where Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) was recommended in 2012 by WHO. This strategy is now implemented widely and protected more than 19 million children in 2018. It was previously reported that exposure to SMC reduced antibody levels to AMA1, MSP-1 42 and CSP, but the duration of exposure to SMC up to three 3 years, had no effect on antibody levels to MSP-1 42 and CSP. In 2017, a cross-sectional survey was carried out 1 month after the last dose of SMC had been given to children aged 4-5 years randomly selected from areas where SMC had been given for 2 or 4 years during the malaria transmission season. A total of 461 children were enrolled, 242 children in areas where SMC had been implemented for 4 years and 219 children in areas where SMC had been implemented for 2 years. Antibody extracted from dry blood spots was used to measure IgG levels to the malaria antigens CSP, MSP-1 42 and AMA1 by ELISA. The prevalence of antibodies to MSP-1 42 was similar in children who had received SMC for 4 years compared to those who had received SMC for only 2 years (85.1 vs 86.0%, ajusted odd ratio (aOR) = 1.06, 95% confidence intervals (CI 0.62-1.80), p = 0.80). The prevalence of antibodies to AMA-1 and to CSP was not lower in children who received SMC for 4 years compared to those who had received SMC for only 2 years (95.3 vs 88.8%, aOR = 3.16, 95% CI 1.44-6.95, p = 0.004 for AMA-1; and 91.2 vs 81.9%, aOR = 3.14, 95% CI 1.70-5.76, p < 0.001 for CSP). Median antibody levels for anti-MSP-1 42 IgG were not significatively inferior in children who had received SMC for four rather than 2 years (0.88 (IQR: 0.64-1.15) and 0.95 ((0.68-1.15), respectively), anti-CSP (1.30 (1.00-1.56) and 1.17 (0.87-1.47)), and anti-AMA-1 (1.45 (1.24-1.68) and 1.41 (1.17-1.64) ). In an area of high seasonal malaria transmission, children who had received SMC for 4 years did not had lower seropositivity or antibody levels to AMA1, MSP-1 42 and CSP compared to children who had received SMC for © The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article' The health information system in Mali reported that in 2018 malaria was responsible for 32% of all outpatient consultations in health facilities with 2.34 million clinical cases of malaria [1] . Since 2012, Seasonal Malaria Chemoprevention (SMC) has been recommended by the World Health Organization (WHO) for children aged 3-59 months living in areas of highly seasonal malaria transmission in this sub-region [2] . SMC consists of full treatment courses of sulfadoxine-pyrimethamine plus amodiaquine (SP + AQ) given to children 3-59 months of age, at monthly intervals during the malaria transmission season to maintain therapeutic anti-malarial drug concentrations in the blood throughout the period of greatest malaria risk [2] . In 2018, 19 million children in 12 countries in Africa's Sahel sub-region were protected through SMC programmes [3] . Despite the substantial benefits provided by SMC, one area of concern is that SMC will impair the natural acquisition of protective immune responses, thereby increasing the risk of disease in later years. Serological markers can be used to monitoring malaria immunity in areas where control intervention efforts have been undertaken. They also provide useful baseline information about the intensity of malaria transmission in different epidemiological situations. Early studies of SMC showed small increases in clinical malaria following the cessation of a single year of the intervention in Mali and Burkina Faso [4, 5] . In Mozambique, antibody levels to Plasmodium falciparum erythrocytic-stage antigens in the first 2 years of life were not different after chemoprophylaxis with SP administered at 3, 4 and 9 months of age [6] . In Senegal, seropositivity to the blood-stage antigens AMA-1 and GLURP were higher in children in areas where SMC was not implemented compared to those in the area where it was implemented although there was no significant difference between children who did or did not receive SMC in the area where the strategy was implemented [7] . In a high-transmission setting in Uganda, children randomly assigned to receive monthly chemoprevention with dihydroartemisinin-piperaquine had a greater percentage of infected red blood cells specific CD4 + T cells coproducing IL-2 and TNF, w
Keywords Extracted from PMC Text: SMC children 3–59 SIGMA FAST GLURP Mali High-binding 96-well AQ Immunoglobulin G MSP-1 blood WBC/μL. red blood cells clone children phosphate buffered saline amodiaquine 6–8 Gambia dapsone 250/12.5 recombinant AMA-1 IL-2 − IgG 's Sahel azithromycin pyrimethamine Senegal [18] CD4 dihydroartemisinin-piperaquine sulfadoxine–pyrimethamine Pichia pastoris [1] blood samples recombinant P. falciparum 3D7 tablet AMA-1 antigen Fig. 1 IL-10/ Tween SP + AQ Niger [9 Escherichia coli [13 IgG antibodies anti-malarials Burkina Faso [4 blood cells ODs TNF AMA1) antigens Plasmodium falciparum erythrocytic-stage antigens Senegal [7 microscopist sera serum hyperimmune serum AMA1 saponin Ouelessebougou malaria-naïve HBX4 P. falciparum Anti-AMA1 MSP-119 WBCs MSP-142 TNF-α P. falciparum antigens plasmodial antigens Anti-CSP
Extracted PMC Text Content in Record: First 5000 Characters:The health information system in Mali reported that in 2018 malaria was responsible for 32% of all outpatient consultations in health facilities with 2.34 million clinical cases of malaria [1]. Since 2012, Seasonal Malaria Chemoprevention (SMC) has been recommended by the World Health Organization (WHO) for children aged 3–59 months living in areas of highly seasonal malaria transmission in this sub-region [2]. SMC consists of full treatment courses of sulfadoxine–pyrimethamine plus amodiaquine (SP + AQ) given to children 3–59 months of age, at monthly intervals during the malaria transmission season to maintain therapeutic anti-malarial drug concentrations in the blood throughout the period of greatest malaria risk [2]. In 2018, 19 million children in 12 countries in Africa's Sahel sub-region were protected through SMC programmes [3]. Despite the substantial benefits provided by SMC, one area of concern is that SMC will impair the natural acquisition of protective immune responses, thereby increasing the risk of disease in later years. Serological markers can be used to monitoring malaria immunity in areas where control intervention efforts have been undertaken. They also provide useful baseline information about the intensity of malaria transmission in different epidemiological situations. Early studies of SMC showed small increases in clinical malaria following the cessation of a single year of the intervention in Mali and Burkina Faso [4, 5]. In Mozambique, antibody levels to Plasmodium falciparum erythrocytic-stage antigens in the first 2 years of life were not different after chemoprophylaxis with SP administered at 3, 4 and 9 months of age [6]. In Senegal, seropositivity to the blood-stage antigens AMA-1 and GLURP were higher in children in areas where SMC was not implemented compared to those in the area where it was implemented although there was no significant difference between children who did or did not receive SMC in the area where the strategy was implemented [7]. In a high-transmission setting in Uganda, children randomly assigned to receive monthly chemoprevention with dihydroartemisinin-piperaquine had a greater percentage of infected red blood cells specific CD4 + T cells coproducing IL-2 and TNF, which were associated with protection from subsequent malaria and parasitaemia, and fewer CD4 + T cells coproducing IL-10/ IFN-γ, which were associated with an increased risk of malaria than control children [8]. A lower prevalence of seropositivity for MSP-119 was reported in children, who received biannual azithromycin preventive treatment compared to whose who received annual treatment in Niger [9]. In a recent study in Ouelessebougou, an area of high seasonal malaria transmission in Mali, the measurement of seroprevalence was less sensitive than measuring IgG levels in detecting differences between children who did or did not receive SMC. Exposure to SMC reduced antibody levels to AMA1, MSP-142 and CSP, but the duration of exposure to SMC up to three 3 years, had no effect on antibody levels to MSP-142 and CSP [10]. The study compared findings in children who never received SMC and those who received it for one, two or three years. In the study reported in this paper, the impact of 4 years of SMC compared to 2 years of SMC on the acquisition of antibodies to malaria antigens was assessed. Seropositivity and antibody levels to pre-erythrocytic stage (CSP) and blood stage (MSP-142, AMA1) antigens were measured in the two groups and compared. The study was conducted in the health district of Ouelessebougou, located 80 km south of Bamako, Mali. The target population was children aged 3 to 59 months of age. SMC was implemented progressively in the district of Ouelessebougou as described previously [10]. Briefly, eight of the 13 sub-districts of Ouelessebougou were randomly selected to receive SMC progressively each year, four in 2014 (year 1) two in 2015 (year 2) and two in 2016 (year 3). In 2016, SMC was extended to the entire district by the National Malaria Control Programme (NMCP). Children in the selected areas received three rounds of SMC in the first year, and four rounds of SMC in the following years. Doses of SMC were given per age according to the WHO recommendation. Children aged 3–11 months received 75 mg of AQ given once daily for 3 days plus a single dose of 250/12.5 mg of SP, while children aged 12–59 months received 150 mg AQ base given once daily for 3 days and a single dose of 500/25 mg of SP. The single dose of SP was given on the first day at the same time as the first dose of AQ. SMC was administrated during the peak malaria transmission at monthly interval for 3 months in 2014 and 4 months the following years. At each cycle the proportion of children who received SMC was estimated to 77 to 90% [11]. To assess the effect of SMC on the acquisition of antibodies to P. falciparum antigens, a cross-sectional survey was conducted at the end of malaria transmission season in Januar
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