Antibody responses to <i>P. falciparum</i> blood stage antigens and incidence of clinical malaria in children living in endemic area in Burkina Faso

Abstract Background High parasite-specific antibody levels are generally associated with low susceptibility to Plasmodium falciparum malaria. This has been supported by several studies in which clinical malaria cases of P. falciparum malaria were reported to be associated with low antibody avidities. This study was conducted to evaluate the role of age, malaria transmission intensity and incidence of clinical malaria in the induction of protective humoral immune response against P. falciparum malaria in children living in Burkina Faso. Methods We combined levels of IgG and IgG subclasses responses to P. falciparum antigens: Merozoite Surface Protein 3 (MSP3), Merozoite Surface Protein 2a (MSP2a), Merozoite Surface Protein 2b (MSP2b), Glutamate Rich Protein R0 (GLURP R0) and Glutamate Rich Protein R2 (GLURP R2) in plasma samples from 325 children under five (05) years with age, malaria transmission season and malaria incidence. Results We notice higher prevalence of P. falciparum infection in low transmission season compared to high malaria transmission season. While, parasite density was lower in low transmission than high transmission season. IgG against all antigens investigated increased with age. High levels of IgG and IgG subclasses to all tested antigens except for GLURP R2 were associated with the intensity of malaria transmission. IgG to MSP3, MSP2b, GLURP R2 and GLURP R0 were associated with low incidence of malaria. All IgG subclasses were associated with low incidence of P. falciparum malaria, but these associations were stronger for cytophilic IgGs. Conclusions On the basis of the data presented in this study, we conclude that the induction of humoral immune response to tested malaria antigens is related to age, transmission season level and incidence of clinical malaria

Single low dose primaquine to reduce gametocyte carriage and Plasmodium falciparum transmission after artemether-lumefantrine in children with asymptomatic infection: a randomised, double-blind, placebo-controlled trial

Background: A single low dose (0.25 mg/kg) of primaquine is recommended as a gametocytocide in combination with artemisinin-based combination therapies for Plasmodium falciparum but its effect on post-treatment gametocyte circulation and infectiousness to mosquitoes has not been quantified. Methods: In this randomised, double-blind, placebo-controlled trial, 360 asymptomatic parasitaemic children aged 2-15 years were enrolled and assigned to receive: artemether-lumefantrine (AL) and a dose of placebo; AL and a 0.25 mg/kg primaquine dose; or AL and a 0.40 mg/kg primaquine dose. On days 0, 2, 3, 7, 10 and 14, gametocytes were detected and quantified by microscopy, Pfs25 mRNA quantitative nucleic acid sequence based amplification (QT-NASBA), and quantitative reverse-transcriptase PCR (qRT-PCR). For a subset of participants, pre- and post-treatment infectiousness was assessed by mosquito feeding assays on days -1, 3, 7, 10 and 14. Results: Both primaquine arms had lower gametocyte prevalences after day 3 compared to the placebo arm, regardless of gametocyte detection method. The mean (95 % confidence interval) number of days to gametocyte clearance in children with patent gametocytes on day 0 (N = 150) was 19.7 (14.6 – 24.8), 7.7 (6.3 – 9.1) and 8.2 (6.7 – 9.6) for the AL-placebo, the 0.25 mg/kg primaquine dose and the 0.40 mg/kg primaquine dose arms, respectively. While 38.0 % (30/79) of selected gametocytaemic individuals were infectious before treatment, only 1/251 participant, from the AL-placebo group, infected mosquitoes after treatment. Conclusions: We observed similar gametocyte clearance rates after 0.25 and 0.40 mg/kg primaquine doses. Infectivity to mosquitoes after AL was very low and absent in primaquine arms

IMMUNE RESPONSES TO HELMINTH PARASITE ANTIGENS IN MALARIA ENDEMIC POPULATIONS

Co-infection with P. falciparum and helminths in Sub-Saharan Africa could modulate the immune response towards the parasites as well as the individual susceptibility to clinical forms. Our aim is to investigate the impact of helminth infections on immune responses and susceptibility to malaria in different ethnic groups from Burkina Faso (Modiano et al. PNAS 1996). The objectives of this work are: i) to measure immunoglobulins against helminth parasite antigens in plasma samples (N=288) collected among Mossi, Fulani and Rimaibe rural communities; ii) to assess differences in relation to age, sex, village, ethnic group, infection with P. falciparum; iii) to assess correlation with antibodies against malaria antigens (CSP, MSP1, MSP2, AMA1) and total IgE. Measurements of IgG against Strongyloides, Taenia spp. and filarial infections are ongoing. A custom ELISA protocol was used to measure IgG against Schistosoma haematobium Soluble Egg Antigen (SEA). The prevalence of anti-SEA IgG is 63%, in line with the prevalence of S. haematobium infection reported for the same area of Burkina Faso (55-85%, Traore et al. Medecine d'Afrique Noire 1990). The prevalence is zero in infants, increases during childhood to reach its peak in teens, and decreases from 20 years onwards. Females show a lower prevalence than males (P=0.003). Differences in prevalence are not observed among villages or ethnic groups, but the Fulani show lower levels of anti-SEA IgG (P=0.0001) suggesting that lighter S. haematobium infections occur in the ethnic group known for a marked lower susceptibility to P. falciparum. Individuals infected with P. falciparum show higher levels of anti-SEA IgG (P=0.0002). A positive correlation exist between anti-SEA IgG, total IgE (P<0.0001) and anti-CSP IgG (P=0.009). These results suggest that common host factors may affect susceptibility to P. falciparum and S. haematobium (e.g. age, ethnicity) and warrant further investigation into the immunological cross-talk between the two parasites

Antibody responses to helminth parasite antigens in malaria endemic populations.

Introduction Co-infection with P. falciparum and helminths in Sub-Saharan Africa could modulate the immune response towards the parasites as well as susceptibility to disease (Salgame et al. Nat Rev Immunol 2013). Our aim is to investigate the impact of helminth infections on the different immunity to malaria shown by ethnic groups from Burkina Faso (Modiano et al. PNAS 1996). Specific objectives are: i) to measure immunoglobulins against helminth parasite antigens in plasma samples collected among Mossi, Fulani and Rimaibe populations; ii) to assess differences in prevalences and levels of specific IgG in relation to age, sex, village, ethnic group, and infection with P. falciparum. Material and methods Plasma samples were collected during a cross-sectional survey conducted in August 2007 in rural villages of Burkina Faso. A subset of samples (N=288) was assayed by ELISA to measure IgG against: i) Strongyloides stercoralis antigens (Bordier Affinity); ii) filarial nematodes antigens (Bordier Affinity) iii) Schistosoma haematobium Soluble Egg Antigen (SEA, Mutapi et al. Paras Immunol 1997). Results The prevalence of IgG against antigens of Strongyloides stercoralis, filarial nematodes and Schistosoma hematobium is 5%, 16%, 63% respectevely. These measures lye within the infection prevalence ranges as obtained by direct diagnosis, suggesting ELISA may be suitable for population screening and evaluation of control programmes. The prevalence of anti-SEA IgG is zero in infants, increases during childhood to reach its peak in teens, and decreases from 20 years onwards. Females show a lower prevalence than males (P=0.003). Differences in prevalence are not observed among villages or ethnic groups, but the Fulani show lower levels of anti-SEA IgG (P=0.0001) indicating that lighter S. haematobium infections may occur in the ethnic group known for a marked lower susceptibility to P. falciparum. Individuals infected with P. falciparum show higher levels of anti-SEA IgG (P=0.0002) suggesting that common host factors may affect susceptibility to P. falciparum and S. haematobium (e.g. age, ethnicity). Conclusions Experimental models indicate that helminths Excretory/Secretory molecules induce Dendritic Cells to produce immunoregulatory cytokines (TGFβ, IL10) promoting the expansion of Tregulatory cells (Tregs) and the suppression of effector responses against intracellular pathogens such as malaria (Salgame et al. Nat Rev Immunol 2013). The malaria resistant Fulani population have been previously described to show lower levels of TGFβ and lower number of Tregs (Torcia et al. PNAS 2008). The observation of lower anti-SEA IgG levels in the Fulani warrants further investigation into the immunological cross-talk between S. haematobium and P. falciparum in this population