Browsing by Author "Massougbodji, A."
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Item Afucosylated Plasmodium falciparum-specific IgG is induced by infection but not by subunit vaccination(NATURE COMMUNICATIONS, 2021) Larsen, M.D.; Lopez-Perez, M.; Dickson, E.K.; Ampomah, P.; Ederveen, H.; Koeleman, C.A.M.; Nouta, J.; Ndam, T.; Mordmüller, B.; Salanti, A.; Nielsen, M.A.; Massougbodji, A.; Schoot, C.E.; Ofori, M.F.; Wuhrer, M.; Hviid, L.; Vidarsson, G.Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family members mediate receptor- and tissue-specific sequestration of infected erythrocytes (IEs) in malaria. Antibody responses are a central component of naturally acquired malaria immunity. PfEMP1-specific IgG likely protects by inhibiting IE sequestration and through IgG-Fc Receptor (FcγR) mediated phagocytosis and killing of antibody-opsonized IEs. The affinity of afucosylated IgG to FcγRIIIa is up to 40-fold higher than fucosylated IgG, resulting in enhanced antibodydependent cellular cytotoxicity. Most IgG in plasma is fully fucosylated, but afucosylated IgG is elicited in response to enveloped viruses and to paternal alloantigens during pregnancy. Here we show that naturally acquired PfEMP1-specific IgG is strongly afucosylated in a stable and exposure-dependent manner, and efficiently induces FcγRIIIa-dependent natural killer (NK) cell degranulation. In contrast, immunization with a subunit PfEMP1 (VAR2CSA) vaccine results in fully fucosylated specific IgG. These results have implications for understanding protective natural- and vaccine-induced immunity to malaria.Item Dynamics of Plasmodium falciparum gametocyte carriage in pregnant women under intermittent preventive treatment with sulfadoxine–pyrimethamine in Benin(Malaria Journal, 2018-10) Jafari-Guemouri, S.; Dhiab, J.; Massougbodji, A.; Deloron, P.; Tuikue, N.N.Background In sub-Saharan Africa, malaria is a major cause of morbidity and mortality, in particular in children and pregnant women. During pregnancy, Plasmodium falciparum infected red blood cells expressing VAR2CSA are selected from circulation by selective cytoadherence to chondroitin sulfate proteoglycan receptors expressed in the placenta, leading to an increased susceptibility to malaria, long-lasting infections and poor pregnancy outcome. Partly because of these long-lasting infections, women were reported to have a higher density of gametocytes in their peripheral blood, and are considered as a potential reservoir for malaria transmission. To improve pregnancy outcome in areas of high malaria transmission, The WHO recommends intermittent preventive treatment with sulfadoxine/pyrimethamine (IPTp-SP) during antenatal care visits. The effect of IPTp-SP on gametocyte carriage in infected pregnant women was studied. Methods The levels of transcription of three gametocytes stage-specific genes Pfs16 (expressed by sexually-committed ring stage parasites and fully matured gametocytes), Pfs25 (expressed by female mature gametocytes) and Pfs230 (expressed by male mature gametocytes) were assessed by real-time PCR in 50 P. falciparum infected women at early pregnancy (before implementation of IPTp-SP), and in 50 infected women at delivery. Sex ratios of male and female gametocytes were determined in these women to assess the effect of IPTp-SP on the gametocyte populations. Results The data show that the three transcript types specific to Pfs16, Pfs25 and Pfs230 were detected in all samples, both at inclusion and delivery. Levels of Pfs25 and Pfs230 transcripts were higher at delivery than at inclusion (p = 0.042 and p = 0.003), while the opposite was observed for Pfs16 (p = 0.048). The ratio of male/female gametocyte transcript levels was higher at delivery than at inclusion (p = 0.018). Since a mixed gender late stage gametocyte culture was used as a positive control, male and female gametocytes could not be quantified in an absolute way in the samples. However, the amplification reliability of the Pfs25 and Pfs230 markers in the samples could be checked. A relative quantity of each type of Pfs transcript was, therefore, used to calculate the sex ratio proxy. Conclusion This study demonstrates that IPTp-SP treatment contributes to modify the parasite populations’ structure during pregnancy. In line with previous studies, we suggest that the continued use of SP in pregnant women as IPTp, despite having a beneficial effect on the pregnancy outcome, could be a risk factor for increased transmission. This reinforces the need for an alternative to the SP drug for malaria prevention during pregnancy.Item The effect of dose on the antimalarial efficacy of artemether-lumefantrine: A systematic review and pooled analysis of individual patient data(The Lancet Infectious Diseases, 2015-06) Anstey, N.M.; Price, R.N.; Davis, T.M.E.; Karunajeewa, H.A.; Mueller, I.; D'Alessandro, U.; Massougbodji, A.; Nikiema, F.; Ouédraogo, J.-B.; Tinto, H.; Zongo, I.; Same-Ekobo, A.; Koné, M.; Menan, H.; Yavo, W.; Touré, A.O.; Kofoed, P.-E.; Alemayehu, B.H.; Jima, D.; Baudin, E.; Espié, E.; Nabasumba, C.; Pinoges, L.; Schramm, B.; Cot, M.; Deloron, P.; Faucher, J.-F.Background: Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. Methods: We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. Findings: We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose). Interpretation: The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups. Funding: Bill & Melinda Gates Foundation. © 2015 Elsevier Ltd.Item Meningococcal immunisation in Ghana(Lancet, 2000) De Chabalier, F.; Chippaux, J.P.; Massougbodji, A.; McDamien, D.; Boelaert, M.; Van Damme, W.; Rosenstein, N.E.Item Persistent Plasmodium falciparum Infection in Women With an Intent to Become Pregnant as a Risk Factor for Pregnancy-associated Malaria(Clinical Infectious Diseases, 2018-11) Ndam, N.T.; Tornyigah, B.; Dossou, A.Y.; Escriou, G.; Nielsen, M.A.; Salanti, A.; Issifou, S.; Massougbodji, A.; Chippaux, J.P.; Deloron, P.Background: Pregnant women are more susceptible to Plasmodium falciparum than before pregnancy, and infection has consequences for both mother and offspring. The World Health Organization recommends that pregnant woman in areas of transmission receive intermittent preventive treatment (IPTp) starting in the second trimester. Consequently, women are not protected during the first trimester, although P. falciparum infections are both frequent and harmful. Methods: A cohort of nulligravid women was followed up during subsequent pregnancy. Malaria was diagnosed by means of microscopy and polymerase chain reaction. Parasites were genotyped at polymorphic loci. Results: Among 275 nulligravidae enrolled, 68 women became pregnant and were followed up during pregnancy. Before pregnancy, P. falciparum prevalence rates were 15% by microscopy and 66% by polymerase chain reaction. Microscopic infection rates increased to 29% until IPTp administration, and their density increased by 20-fold. Conversely, submicroscopic infection rates decreased. After IPTp administration, all types of infections decreased, but they increased again late in pregnancy. The risk of infection during pregnancy was higher in women with a microscopic (odds ratio, 6.5; P = .047) or submicroscopic (3.06; P = .05) infection before pregnancy and was not related to the season of occurrence. Most infections during pregnancy were persistent infections acquired before pregnancy. Conclusions: Microscopic and submicroscopic malaria infections were frequent in nulligravid women from south Benin. During the first trimester of pregnancy, microscopic infections were more frequent, with a higher parasite density, and mainly derived from parasites infecting the woman before conception. Preventive strategies targeting nonpregnant women with a desire for conception need to be designed.Item Submicroscopic placental infection by non-falciparum Plasmodium spp(PLoS Neglected Tropical Diseases, 2018-02) Doritchamou, J.Y.A.; Akuffo, R.A.; Moussiliou, A.; Luty, A.J.F.; Massougbodji, A.; Deloron, P.; Tuikue Ndam, N.G.Background: Among the Plasmodium species that infect humans, adverse effects of P. falciparum and P. vivax have been extensively studied and reported with respect to poor outcomes particularly in first time mothers and in pregnant women living in areas with unstable malaria transmission. Although, other non-falciparum malaria infections during pregnancy have sometimes been reported, little is known about the dynamics of these infections during pregnancy. Methods and findings: Using a quantitative PCR approach, blood samples collected from Beninese pregnant women during the first antenatal visit (ANV) and at delivery including placental blood were screened for Plasmodium spp. Risk factors associated with Plasmodium spp. infection during pregnancy were assessed as well as the relationships with pregnancy outcomes. P. falciparum was the most prevalent Plasmodium species detected during pregnancy, irrespective either of parity, of age or of season during which the infection occurred. Although no P. vivax infections were detected in this cohort, P. malariae (9.2%) and P. ovale (5.8%) infections were observed in samples collected during the first ANV. These non-falciparum infections were also detected in maternal peripheral blood (1.3% for P. malariae and 1.2% for P. ovale) at delivery. Importantly, higher prevalence of P. malariae (5.5%) was observed in placental than peripheral blood while that of P. ovale was similar (1.8% in placental blood). Among the non-falciparum infected pregnant women with paired peripheral and placental samples, P. malariae infections in the placental blood was significantly higher than in the peripheral blood, suggesting a possible affinity of P. malariae for the placenta. However, no assoctiation of non-falciparum infections and the pregnancy outcomes was observed Conclusions: Overall this study provided insights into the molecular epidemiology of Plasmodium spp. infection during pregnancy, indicating placental infection by non-falciparum Plasmodium and the lack of association of these infections with adverse pregnancy outcomes. © 2018 Public Library of Science. All Rights Reserved.