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  • 1. Anchang-Kimbi, Judith K.
    et al.
    Achidi, Eric A.
    Apinjoh, Tobias O.
    Mugri, Regina N.
    Chi, Hanesh Fru
    Tata, Rolland B.
    Nkegoum, Blaise
    Mendimi, Joseph-Marie N.
    Sverremark-Ekström, Eva
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Troye Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Antenatal care visit attendance, intermittent preventive treatment during pregnancy (IPTp) and malaria parasitaemia at delivery2014Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 13, s. 162-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The determinants and barriers for delivery and uptake of IPTp vary with different regions in sub-Saharan Africa. This study evaluated the determinants of ANC clinic attendance and IPTp-SP uptake among parturient women from Mount Cameroon Area and hypothesized that time of first ANC clinic attendance could influence uptake of IPTp-SP/dosage and consequently malaria parasite infection status at delivery. Methods: Two cross sectional surveys were carried out at the Government Medical Centre in the Mutengene Health Area, Mt Cameroon Area from March to October 2007 and June 2008 to April 2009. Consented parturient women were consecutively enrolled in both surveys. In 2007, socio-demographic data, ANC clinic attendance, gestational age, fever history and reported use/dosage of IPTp-SP were documented using a structured questionnaire. In the second survey only IPT-SP usage/dosage was recorded. Malaria parasitaemia at delivery was determined by blood smear microscopy and placental histology. Results and discussion: In 2007, among the 287 women interviewed, 2.2%, 59.7%, and 38.1% enrolled in the first, second and third trimester respectively. About 90% of women received at least one dose SP but only 53% received the two doses in 2007 and by 2009 IPTp-two doses coverage increased to 64%. Early clinic attendance was associated (P = 0.016) with fever history while being unmarried (OR = 2.2; 95% CI: 1.3-3.8) was significantly associated with fewer clinic visits (<4visits). Women who received one SP dose (OR = 3.7; 95% CI: 2.0-6.8) were more likely not to have attended >= 4visits. A higher proportion (P < 0.001) of women with first visit during the third trimester received only one dose, meanwhile, those who had an early first ANC attendance were more likely (OR = 0.4; 95% CI = 0.2 - 0.7) to receive two or more doses. Microscopic parasitaemia at delivery was frequent (P = 0.007) among women who enrolled in the third trimester and had received only one SP dose than in those with two doses. Conclusion: In the study area, late first ANC clinic enrolment and fewer clinic visits may prevent the uptake of two SP doses and education on early and regular ANC clinic visits can increase IPTp coverage.

  • 2. Anchang-Kimbi, Judith K
    et al.
    Achidi, Eric A
    Nkegoum, Blaise
    Sverremark-Ekström, Eva
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Diagnostic comparison of malaria infection in peripheral blood, placental blood and placental biopsies in Cameroonian parturient women.2009Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 8, s. 126-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: In sub-Saharan Africa, Plasmodium falciparum malaria in pregnancy presents an enormous diagnostic challenge. The epidemiological and clinical relevance of the different types of malaria diagnosis as well as risk factors associated with malaria infection at delivery were investigated. METHOD: In a cross-sectional survey, 306 women reporting for delivery in the Mutenegene maternity clinic, Fako division, South West province, Cameroon were screened for P. falciparum in peripheral blood, placental blood and placental tissue sections by microscopy. Information relating to the use of intermittent preventive treatment in pregnancy with sulphadoxine/pyrimethamine, history of fever attack, infant birth weights and maternal anaemia were recorded. RESULTS: Among these women, P. falciparum infection was detected in 5.6%, 25.5% and 60.5% of the cases in peripheral blood, placental blood and placental histological sections respectively. Placental histology was more sensitive (97.4%) than placental blood film (41.5%) and peripheral blood (8.0%) microscopy. In multivariate analysis, age (< or = 20 years old) (OR = 4.61, 95% CI = 1.47 - 14.70), history of fever attack (OR = 2.98, 95% CI = 1.58 - 5.73) were significant risk factors associated with microscopically detected parasitaemia. The use of > or = 2 SP doses (OR = 0.18, 95% CI = 0.06 - 0.52) was associated with a significant reduction in the prevalence of microscopic parasitaemia at delivery. Age (>20 years) (OR = 0.34, 95% CI = 0.15 - 0.75) was the only significant risk factor associated with parasitaemia diagnosed by histology only in univariate analysis. Microscopic parasitaemia (OR = 2.74, 95% CI = 1.33-5.62) was a significant risk factor for maternal anaemia at delivery, but neither infection detected by histology only, nor past infection were associated with increased risk of anaemia. CONCLUSION: Placenta histological examination was the most sensitive indicator of malaria infection at delivery. Microscopically detected parasitaemia was associated with increased risk of maternal anaemia at delivery, but not low-grade parasitaemia detected by placental histology only.

  • 3.
    Boström, Stephanie
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Giusti, Pablo
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Arama, Charles
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut. University of Bamako, Mali.
    Persson, Jan-Olov
    Stockholms universitet, Naturvetenskapliga fakulteten, Matematiska institutionen.
    Dara, Victor
    Traore, Boubacar
    Dolo, Amagana
    Doumbo, Ogobara
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Changes in the levels of cytokines, chemokines and malaria specific antibodies in response to Plasmodium falciparum infection in children living in sympatry in Mali2012Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 11, s. 109-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The Fulani are known to be less susceptible to Plasmodium falciparum malaria as reflected by lower parasitaemia and fewer clinical symptoms than other sympatric ethnic groups. So far most studies in these groups have been performed on adults, which is why little is known about these responses in children. This study was designed to provide more information on this gap. Methods: Circulating inflammatory factors and antibody levels in children from the Fulani and Dogon ethnic groups were measured. The inflammatory cytokines; interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12p70, tumor necrosis factor (TNF) and the chemokines; regulated on activation normal T cell expressed and secreted (RANTES), monokine-induced by IFN-gamma (MIG), monocyte chemotactic protein (MCP)-1 and IFN-gamma-inducible protein (IP)-10 were measured by cytometric bead arrays. The levels of interferon (IFN)-alpha, IFN-gamma and malaria-specific antibodies; immunoglobulin (Ig) G, IgM and IgG subclasses (IgG1-IgG4) were measured by ELISA. Results: The results revealed that the Fulani children had higher levels of all tested cytokines compared to the Dogon, in particular IFN-gamma, a cytokine known to be involved in parasite clearance. Out of all the tested chemokines, only MCP-1 was increased in the Fulani compared to the Dogon. When dividing the children into infected and uninfected individuals, infected Dogon had significantly lower levels of RANTES compared to their uninfected peers, and significantly higher levels of MIG and IP-10 as well as MCP-1, although the latter did not reach statistical significance. In contrast, such patterns were not seen in the infected Fulani children and their chemokine levels remained unchanged upon infection compared to uninfected counterparts. Furthermore, the Fulani also had higher titres of malaria-specific IgG and IgM as well as IgG1-3 subclasses compared to the Dogon. Conclusions: Taken together, this study demonstrates, in accordance with previous work, that Fulani children mount a stronger inflammatory and antibody response against P. falciparum parasites compared to the Dogon and that these differences are evident already at an early age. The inflammatory responses in the Fulani were not influenced by an active infection which could explain why less clinical symptoms are seen in this group.

  • 4. Chen, Tzu Tung
    et al.
    Charpentier Ljungqvist, Fredrik
    Stockholms universitet, Humanistiska fakulteten, Historiska institutionen. Swedish Collegium for Advanced Study, Sweden.
    Castenbrandt, Helene
    Hildebrandt, Franziska
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Mølbak Ingholt, Mathias
    Hesson, Jenny C.
    Ankarklev, Johan
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Seftigen, Kristina
    Linderholm, Hans W.
    The spatiotemporal distribution of historical malaria cases in Sweden: a climatic perspective2021Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 20, nr 1, artikel-id 212Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Understanding of the impacts of climatic variability on human health remains poor despite a possibly increasing burden of vector-borne diseases under global warming. Numerous socioeconomic variables make such studies challenging during the modern period while studies of climate-disease relationships in historical times are constrained by a lack of long datasets. Previous studies have identified the occurrence of malaria vectors, and their dependence on climate variables, during historical times in northern Europe. Yet, malaria in Sweden in relation to climate variables is understudied and relationships have never been rigorously statistically established. This study seeks to examine the relationship between malaria and climate fluctuations, and to characterise the spatio-temporal variations at parish level during severe malaria years in Sweden 1749-1859.

    Methods: Symptom-based annual malaria case/death data were obtained from nationwide parish records and military hospital records in Stockholm. Pearson (r(p)) and Spearman's rank (r(s)) correlation analyses were conducted to evaluate inter-annual relationship between malaria data and long meteorological series. The climate response to larger malaria events was further explored by Superposed Epoch Analysis, and through Geographic Information Systems analysis to map spatial variations of malaria deaths.

    Results: The number of malaria deaths showed the most significant positive relationship with warm-season temperature of the preceding year. The strongest correlation was found between malaria deaths and the mean temperature of the preceding June-August (r(s) = 0.57, p < 0.01) during the 1756-1820 period. Only non-linear patterns can be found in response to precipitation variations. Most malaria hot-spots, during severe malaria years, concentrated in areas around big inland lakes and southern-most Sweden.

    Conclusions: Unusually warm and/or dry summers appear to have contributed to malaria epidemics due to both indoor winter transmission and the evidenced long incubation and relapse time of P. vivax, but the results also highlight the difficulties in modelling climate-malaria associations. The inter-annual spatial variation of malaria hot-spots further shows that malaria outbreaks were more pronounced in the southern-most region of Sweden in the first half of the nineteenth century compared to the second half of the eighteenth century.

  • 5. Cherif, Mariama
    et al.
    Amoako-Sakyi, Daniel
    Dolo, Amagana
    Pearson, Jan-Olov
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Gyan, Ben
    Obiri-Yeboah, Dorcas
    Nebie, Issa
    Sirima, Sodiomon B.
    Doumbo, Ogobara
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Bakary, Maiga
    Distribution of Fc gamma R gene polymorphisms among two sympatric populations in Mali: differing allele frequencies, associations with malariometric indices and implications for genetic susceptibility to malaria2016Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 15, artikel-id 29Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Genetic polymorphisms in the complex gene cluster encoding human Fc-gamma receptors (Fc gamma Rs) may influence malaria susceptibility and pathogenesis. Studying genetic susceptibility to malaria is ideal among sympatric populations because the distribution of polymorphic genes among such populations can help in the identification malaria candidate genes. This study determined the distribution of three FcyRs single nucleotide polymorphisms (SNPs) (Fc gamma RIIB-rs1050519, Fc gamma RIIC-rs3933769 and Fc gamma RIIIA-rs396991) among sympatric Fulani and Dogon children with uncomplicated malaria. The association of these SNPs with clinical, malariometric and immunological indices was also tested. Methods: This study involved 242 Fulani and Dogon volunteers from Mali age under 15 years. All SNPs were genotyped with predesigned TaqMan (R) SNP Genotyping Assays. Genotypic and allelic distribution of SNPs was compared across ethnic groups using the Fisher exact test. Variations in clinical, malariometric and immunologic indices between groups were tested with Kruskal-Wallis H, Mann-Whitney U test and Fisher exact test where appropriate. Results: The study confirmed known malariometric and immunologic differences between sympatric Fulani and non-Fulani tribes. Parasite density was lower in the Fulani than the Dogon (p < 0.0001). The mutant allele of Fc gamma RIIC (rs3933769) was found more frequently in the Fulani than the Dogon (p < 0.0001) while that of Fc gamma RIIIA (rs396991) occurred less frequently in the Fulani than Dogon (p = 0.0043). The difference in the mutant allele frequency of Fc gamma RIIB (rs1050519) between the two ethnic groups was however not statistically significant (p = 0.064). The mutant allele of rs396991 was associated with high malaria-specific IgG1 and IgG3 in the entire study population and Dogon tribe, p = 0.023 and 0.015, respectively. Parasite burden was lower in carriers of the Fc gamma RIIC (rs3933769) mutant allele than non-carriers in the entire study population (p < 0.0001). Carriers of this allele harboured less than half the parasites found in non-carriers. Conclusion: Differences in the allelic frequencies of rs3933769 and rs396991 among Fulani and Dogon indirectly suggest that these SNPs may influence malaria susceptibility and pathogenesis in the study population. The high frequency of the Fc gamma RIIC (rs3933769) mutant allele in the Fulani and its subsequent association with low parasite burden in the entire study population is noteworthy.

  • 6. Fievet, Nadine
    et al.
    Varani, Stefania
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Ibitokou, Samad
    Briand, Valerie
    Louis, Stephanie
    Perrin, Rene Xavier
    Massougbogji, Achille
    Hosmalin, Anne
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Deloron, Philippe
    Plasmodium falciparum exposure in utero, maternal age and parity influence the innate activation of foetal antigen presenting cells2009Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 8, s. 251-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Malaria in pregnancy is associated with immunological abnormalities in the newborns, such as hampered T-helper 1 responses and increased T-regulatory responses, while the effect of maternal Plasmodium falciparum infection on foetal innate immunity is still controversial. Materials and methods: The immunophenotype and cytokine release by dendritic cells (DC) and monocytes were evaluated in cord blood from 59 Beninese women with or without malaria infection by using flow cytometry. Results: Accumulation of malaria pigment in placenta was associated with a partial maturation of cord blood myeloid and plasmacytoid DC, as reflected by an up-regulated expression of the major histocompatibility complex class II molecules, but not CD86 molecules. Cells of newborns of mothers with malaria pigment in their placenta also exhibited significantly increased cytokine responses upon TLR9 stimulation. In addition, maternal age and parity influenced the absolute numbers and activation status of cord blood antigen-presenting cells. Lastly, maternal age, but not parity, influenced TLR3, 4 and 9 responses in cord blood cells. Discussion: Our findings support the view that placental parasitization, as indicated by the presence of malaria pigment in placental leukocytes, is significantly associated with partial maturation of different DC subsets and also to slightly increased responses to TLR9 ligand in cord blood. Additionally, other factors, such as maternal age and parity should be taken into consideration when analysing foetal/neonatal innate immune responses. Conclusion: These data advocate a possible mechanism by which PAM may modulate foetal/neonatal innate immunity.

  • 7. Gbedande, Komi
    et al.
    Cottrell, Gilles
    Vianou, Bertin
    Ibitokou, Samad
    Fernando, Aurax
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Salanti, Ali
    Moutairou, Kabirou
    Massougbodji, Achille
    Ndam, Nicaise Tuikue
    Deloron, Philippe
    Luty, Adrian J. F.
    Fievet, Nadine
    Infections with Plasmodium falciparum during pregnancy affect VAR2CSA DBL-5 domain-specific T cell cytokine responses2016Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 15, artikel-id 485Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Current knowledge of human immunological responses to pregnancy-associated malaria-specific Plasmodium falciparum protein VAR2CSA concerns almost exclusively B cell-driven antibody-mediated activity. Knowledge of VAR2CSA-specific T cell-mediated activity is minimal by comparison, with only a single published report of a study investigating VAR2CSA-derived peptide-specific T cell responses. The study described here represents an attempt to redress this balance. Methods: Within the framework of a cohort study of 1037 pregnant Beninese, sub-groups were selected on the basis of the documented presence/absence of infection with P. falciparum and conducted detailed immunological assessments both at inclusion into the study and at delivery. Peripheral blood mononuclear cells were isolated, stimulated in vitro, and VAR2CSA DBL-5 domain-specific, IFN-gamma-secreting T-cell frequencies and cytokine responses were quantified using flow cytometric techniques. Multivariate analyses were used to determine primarily whether the T cell-mediated DBL5-specific activity measured was associated with infection by P. falciparum adjusted for gravidity, anaemia and other cofactors. Results: Infections with P. falciparum detected at inclusion were associated with enhanced non-specific TNF responses, whilst diminished non-specific and DBL-5-specific IL-10 responses were associated with infections detected at delivery. Infections during pregnancy led to enhanced non-specific and DBL-5-specific IFN-gamma responses detectable at delivery but to concomitantly lower DBL-5-specific CD8+ IFN-gamma responses. Prospective assessments indicated that non-specific pro-inflammatory responses detectable at inclusion in the study were associated with the occurrence of infections subsequently during pregnancy. Conclusions: The findings represent a first step in elucidating the quantity and quality of cellular immunological responses to VAR2CSA, which will help in the development of the primary vaccine candidate for prevention of pregnancy-associated malaria.

  • 8. Giha, Hayder A.
    et al.
    Nasr, Amre
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Iriemenam, Nnaemeka C.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Arnot, David
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Theander, Thor G.
    Berzins, Klavs
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Elghazali, Gehad
    Pandey, Janardan P.
    Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria.2009Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 8, nr 1, artikel-id 306Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ABSTRACT: BACKGROUND: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control. METHODS: In this study, 216 individuals from Daraweesh, an area of seasonal malaria transmission in Sudan, were followed for nine years for malaria infection. Total IgG and IgG isotypes against four malaria antigens, MSP2-3D7, MSP2-FC27, AMA1, and Pf332-C231 were measured in plasma obtained from the cohort at the end of the study, during the dry malaria-free period. The GM/KM allotypes of the donors were determined. RESULTS: The GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly higher baseline levels of total IgG and non-cytophilic IgG isotypes as compared to non-carriers. The KM allotypes influence on IgG isotypes level was limited. Finally, the differences in the baseline concentrations of total IgG and IgG isotypes between the different GK/KM phenotype carriers were antigen-dependent. DISCUSSION: The results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptible CONCLUSIONS: The GM allotypes have significant influence on susceptibility to uncomplicated P. falciparum malaria and antigen-dependent influence on total IgG and IgG subclasses.

  • 9. Holtel, Andreas
    et al.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Penas-Jimenez, Inmaculada
    EU-funded malaria research under the 6th and 7th Framework Programmes for research and technological development.2011Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 10, s. 11-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    While malaria research has traditionally been strong in Europe, targeted and sustained support for cooperative malaria research at EU level, namely through the EU's 6th and 7th Framework Programmes for research and technological development, FP6 (2002-2006) and FP7 (2007-2013), has boosted both impact and visibility of European malaria research. Most of the European malaria research community is now organized under a number of comprehensive and complementary research networks and projects, assembled around four key areas: (1) fundamental research on the malaria parasite and the disease, (2) development of new malaria drugs, (3) research and development of a malaria vaccine, and (4) research to control the malaria-transmitting mosquito vector. Considerable efforts were undertaken to ensure adequate participation of research groups from disease-endemic countries, in particular from Africa, with the long-term aim to strengthen cooperative links and research capacities in these countries. The concept of organizing European research through major strategic projects to form a "European Research Area" (ERA) was originally developed in the preparation of FP6, and ERA formation has now turned into a major EU policy objective explicitly inscribed into the Lisbon Treaty. EU-funded malaria research may serve as a showcase to demonstrate how ERA formation can successfully be implemented in a given area of science when several surrounding parameters converge to support implementation of this strategic concept: timely coincidence of political stimuli, responsive programming, a clearly defined--and well confined--area of research, and the readiness of the targeted research community who is well familiar with transnational cooperation at EU level. Major EU-funded malaria projects have evolved into thematic and organizational platforms that can collaborate with other global players. Europe may thus contribute more, and better, to addressing the global research agenda for malaria.

  • 10.
    Israelsson, Elisabeth
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Ekström, Mattias
    Nasr, Amre
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Dolo, Amagana
    Kearsley, Susannah
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Arambepola, Gishanthi
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Homann, Manijeh V.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Maiga, Bakary
    Doumbo, Ogobara K.
    ElGhazali, Gehad
    Giha, Hayder A.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Berzins, Klavs
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Tornvall, Per
    Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa2009Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 8, nr 136Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background

    C-reactive protein (CRP) is an acute phase protein that can activate various immune cells and bind to certain Fcγ receptors. The latter may compete with the binding of IgG antibodies to these receptors and could thereby interfere with the antigen-specific immune response. Polymorphisms in the promoter region of the CRP gene have been strongly associated with the plasma concentration of CRP. The known lower susceptibility to malaria in the Fulani ethnic group, as compared to their sympatric neighbours in Africa, has been linked to different genetic backgrounds. The present study was performed to investigate if polymorphisms in the CRP gene could contribute to the lower susceptibility to malaria seen in the Fulani ethnic group.

    Methods

    The CRP -717 T>C, -286 C>T>A, and +1444 C>T polymorphisms were analysed in asymptomatic Fulani and non-Fulani individuals from Mali and Sudan using Pyrosequencing T and TaqMan r MGB probes.

    Results

    The rare -286 A allele, previously shown to be associated with increased CRP expression and plasma levels, was shown to be more frequent in the non-Fulani ethnic groups as compared to the sympatric Fulani ethnic group both in Mali and Sudan. The common -717 T allele was more prevalent in the non-Fulani ethnic group compared to the sympatric Fulani ethnic group, but only in Mali. The parasite prevalence was increased for the -286 A allele, but not for the -717 T allele. No differences regarding genotype frequency or parasite prevalence were seen for +1444 C>T.

    Conclusion

    This study indicate that CRP may play an important role in the immune responses to malaria, and that the -286 C/T/A CRP polymorphism may be a contributing factor to the lower susceptibility to malaria seen in the Fulani.

  • 11.
    Israelsson, Elisabeth
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Vafa, Manijeh
    Maiga, Bakary
    Lysén, Anna
    Iriemenam, Nnaemeka C.
    Dolo, Amagana
    Doumbo, Ogobara K.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Berzins, Klavs
    Differences in Fcγ receptor IIa genotypes and IgG subclass pattern of anti-malarial antibodies between sympatric ethnic groups in Mali2008Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 7, nr 175Artikel i tidskrift (Refereegranskat)
  • 12. Lokki, A Inkeri
    et al.
    Järvelä, Irma
    Israelsson, Elisabeth
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Maiga, Bakary
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Dolo, Amagana
    Doumbo, Ogobara K
    Meri, Seppo
    Holmberg, Ville
    Lactase persistence genotypes and malaria susceptibility in Fulani of Mali.2011Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 10, s. 9-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Fulani are a widely spread African ethnic group characterized by lower susceptibility to Plasmodium falciparum, clinical malaria morbidity and higher rate of lactase persistence compared to sympatric tribes. Lactase non-persistence, often called lactose intolerance, is the normal condition where lactase activity in the intestinal wall declines after weaning. Lactase persistence, common in Europe, and in certain African people with traditions of raising cattle, is caused by polymorphisms in the enhancer region approximately 14 kb upstream of the lactase gene.

    METHODS: To evaluate the relationship between malaria and lactase persistence genotypes, a 400 bp region surrounding the main European C/T-13910 polymorphism upstream of the lactase gene was sequenced. DNA samples used in the study originated from 162 Fulani and 79 Dogon individuals from Mali.

    RESULTS: Among 79 Dogon only one heterozygote of the lactase enhancer polymorphism was detected, whereas all others were homozygous for the ancestral C allele. Among the Fulani, the main European polymorphism at locus C/T-13910 was by far the most common polymorphism, with an allele frequency of 37%. Three other single-nucleotide polymorphisms were found with allele frequencies of 3.7%, 1.9% and 0.6% each. The novel DNA polymorphism T/C-13906 was seen in six heterozygous Fulani. Among the Fulani with lactase non-persistence CC genotypes at the C/T-13910 locus, 24% had malaria parasites detectable by microscopy compared to 18% for lactase persistent genotypes (P = 0.29). Pooling the lactase enhancer polymorphisms to a common presumptive genotype gave 28% microscopy positives for non-persistent and 17% for others (P = 0.11).

    CONCLUSIONS: Plasmodium falciparum parasitaemia in asymptomatic Fulani is more common in individuals with lactase non-persistence genotypes, but this difference is not statistically significant. The potential immunoprotective properties of dietary cow milk as a reason for the partial malaria resistance of Fulani warrant further investigation.

  • 13.
    Maiga, Bakary
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Universités de Bamako, Bali.
    Dolo, Amagana
    Campino, Susana
    Sepulveda, Nuno
    Corran, Patrick
    Rockett, Kirk A.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Doumbo, Ogobara K.
    Clark, Taane G.
    Glucose-6-phosphate dehydrogenase polymorphisms and susceptibility to mild malaria in Dogon and Fulani, Mali2014Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 13, s. 270-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is associated with protection from severe malaria, and potentially uncomplicated malaria phenotypes. It has been documented that G6PD deficiency in sub-Saharan Africa is due to the 202A/376G G6PD A-allele, and association studies have used genotyping as a convenient technique for epidemiological studies. However, recent studies have shown discrepancies in G6PD202/376 associations with severe malaria. There is evidence to suggest that other G6PD deficiency alleles may be common in some regions of West Africa, and that allelic heterogeneity could explain these discrepancies. Methods: A cross-sectional epidemiological study of malaria susceptibility was conducted during 2006 and 2007 in the Sahel meso-endemic malaria zone of Mali. The study included Dogon (n = 375) and Fulani (n = 337) sympatric ethnic groups, where the latter group is characterized by lower susceptibility to Plasmodium falciparum malaria. Fifty-three G6PD polymorphisms, including 202/376, were genotyped across the 712 samples. Evidence of association of these G6PD polymorphisms and mild malaria was assessed in both ethnic groups using genotypic and haplotypic statistical tests. Results: It was confirmed that the Fulani are less susceptible to malaria, and the 202A mutation is rare in this group (< 1% versus Dogon 7.9%). The Betica-Selma 968C/376G (similar to 11% enzymatic activity) was more common in Fulani (6.1% vs Dogon 0.0%). There are differences in haplotype frequencies between Dogon and Fulani, and association analysis did not reveal strong evidence of protective G6PD genetic effects against uncomplicated malaria in both ethnic groups and gender. However, there was some evidence of increased risk of mild malaria in Dogon with the 202A mutation, attaining borderline statistical significance in females. The rs915942 polymorphism was found to be associated with asymptomatic malaria in Dogon females, and the rs61042368 polymorphism was associated with clinical malaria in Fulani males. Conclusions: The results highlight the need to consider markers in addition to G6PD202 in studies of deficiency. Further, large genetic epidemiological studies of multi-ethnic groups in West Africa across a spectrum of malaria severity phenotypes are required to establish who receives protection from G6PD deficiency.

  • 14. Minja, Daniel T. R.
    et al.
    Schmiegelow, Christentze
    Oesterholt, Mayke
    Magistrado, Pamela A.
    Boström, Stephanie
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    John, Davis
    Pehrson, Caroline
    Andersen, Daniel
    Deloron, Philippe
    Salanti, Ali
    Lemnge, Martha
    Luty, Adrian J. F.
    Alifrangis, Michael
    Theander, Thor
    Lusingu, John P. A.
    Reliability of rapid diagnostic tests in diagnosing pregnancy associated malaria in North Eastern Tanzania2012Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 11, s. 211-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Accurate diagnosis and prompt treatment of pregnancy-associated malaria (PAM) are key aspects in averting adverse pregnancy outcomes. Microscopy is the gold standard in malaria diagnosis, but it has limited detection and availability. When used appropriately, rapid diagnostic tests (RDTs) could be an ideal diagnostic complement to microscopy, due to their ease of use and adequate sensitivity in detecting even sub-microscopic infections. Polymerase chain reaction (PCR) is even more sensitive, but it is mainly used for research purposes. The accuracy and reliability of RDTs in diagnosing PAM was evaluated using microscopy and PCR. Methods: A cohort of pregnant women in north-eastern Tanzania was followed throughout pregnancy for detection of plasmodial infection using venous and placental blood samples evaluated by histidine rich protein 2 (HRP-2) and parasite lactate dehydrogenase (pLDH) based RDTs (Parascreen (TM)) or HRP-2 only (Paracheck Pf (R) and ParaHIT (R) f), microscopy and nested Plasmodium species diagnostic PCR. Results: From a cohort of 924 pregnant women who completed the follow up, complete RDT and microscopy data was available for 5,555 blood samples and of these 442 samples were analysed by PCR. Of the 5,555 blood samples, 49 ((proportion and 95% confidence interval) 0.9% [0.7 - 1.1]) samples were positive by microscopy and 91 (1.6% [1.3-2.0]) by RDT. Forty-six (50.5% [40.5 - 60.6]) and 45 (49.5% [39.4 - 59.5]) of the RDT positive samples were positive and negative by microscopy, respectively, whereas nineteen (42.2% [29.0 - 56.7]) of the microscopy negative, but RDT positive, samples were positive by PCR. Three (0.05% [0.02 - 0.2]) samples were positive by microscopy but negative by RDT. 351 of the 5,461 samples negative by both RDT and microscopy were tested by PCR and found negative. There was no statistically significant difference between the performances of the different RDTs. Conclusions: Microscopy underestimated the real burden of malaria during pregnancy and RDTs performed better than microscopy in diagnosing PAM. In areas where intermittent preventive treatment during pregnancy may be abandoned due to low and decreasing malaria risk and instead replaced with active case management, screening with RDT is likely to identify most infections in pregnant women and out-performs microscopy as a diagnostic tool.

  • 15. Nasr, Amre
    et al.
    Iriemenam, Nnaemeka C.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Giha, Hayder
    Balogun, Halima A.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Anders, Robin F.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    ElGhazali, Gehad
    Berzins, Klavs
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    FcgammaRIIa (CD32) polymorphism and anti-malarial IgG subclass pattern among Fulani and sympatric ethnic groups living in eastern Sudan2009Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 8, nr 43, s. 1-10Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: A SNP at position 131, in the FcgammaRIIa gene, affects the binding of the different IgG subclasses and may influence the clinical variation seen in patients with falciparum malaria. This study confirms and extends previous findings, analysing the FcgammaRIIa (CD32) polymorphism in relation to the IgG subclass distribution seen among two sympatric tribes living in eastern Sudan, characterized by marked differences in susceptibility to Plasmodium falciparum malaria. METHODS: Two hundred and fifty Fulani subjects living in an area of meso-endemic P. falciparum malaria infection were genotyped for the FcgammaRIIa-131 polymorphism. For comparison, 101 non-Fulani donors - (Masaleit, Hausa and Four) - living in the same study area, were genotyped. The levels of plasma antibodies (IgG and subclasses) to four malaria antigens (AMA-1, MSP 2 - 3D7 & FC27, Pf332-C231) were measured using indirect enzyme-linked immunosorbent assays. RESULTS: The FcgammaRIIa-H/H131 genotype was found to be significantly more prevalent in the Fulani as compared to the non-Fulani ethnic groups (36.0% for Fulani versus 17.8% for non-Fulani, adjusted OR 3.10, 95% CI 1.61-5.97, P value < 0.001). The Fulani showed lower anti-malarial IgG1 and IgG3 antibody levels as compared to the non-Fulani and higher levels of IgG2 antibodies. CONCLUSION: The FcgammaRIIa-H/H131 genotype and H131 allele is at higher frequency in the Fulani ethnic group. The H/H131 genotype was consistently associated with higher levels of anti-malarial IgG2 and IgG3 antibodies, while the R/R131 genotype was associated with higher levels of IgG1 antibodies.

  • 16. Okafor, Christian M. F.
    et al.
    Anumudu, Chiaka I.
    Omosun, Yusuf O.
    Uthaipibull, Chairat
    Ayede, Idowu
    Awobode, Henrietta O.
    Odaibo, Alex B.
    Langhorne, Jean
    Holder, Anthony A.
    Nwuba, Roseangela I.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Cellular responses to modified Plasmodium falciparum MSP1(19) antigens in individuals previously exposed to natural malaria infection2009Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 8, s. 263-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: MSP1 processing-inhibitory antibodies bind to epitopes on the 19 kDa C-terminal region of the Plasmodium falciparum merozoite surface protein 1 (MSP1(19)), inhibiting erythrocyte invasion. Blocking antibodies also bind to this antigen but prevent inhibitory antibodies binding, allowing invasion to proceed. Recombinant MSP1(19) had been modified previously to allow inhibitory but not blocking antibodies to continue to bind. Immunization with these modified proteins, therefore, has the potential to induce more effective protective antibodies. However, it was unclear whether the modification of MSP1(19) would affect critical T-cell responses to epitopes in this antigen. Methods: The cellular responses to wild-type MSP1(19) and a panel of modified MSP1(19) antigens were measured using an in-vitro assay for two groups of individuals: the first were malaria-nave and the second had been naturally exposed to Plasmodium falciparum infection. The cellular responses to the modified proteins were examined using cells from malaria-exposed infants and adults. Results: Interestingly, stimulation indices (SI) for responses induced by some of the modified proteins were at least two-fold higher than those elicited by the wild-type MSP1(19). A protein with four amino acid substitutions (Glu27 -> Tyr, Leu31 -> Arg, Tyr34 -> Ser and Glu43 -> Leu) had the highest stimulation index (SI up to 360) and induced large responses in 64% of the samples that had significant cellular responses to the modified proteins. Conclusion: This study suggests that specific MSP1(19) variants that have been engineered to improve their antigenicity for inhibitory antibodies, retain T-cell epitopes and the ability to induce cellular responses. These proteins are candidates for the development of MSP1-based malaria vaccines.

  • 17.
    Perdijk, Olaf
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. Wageningen University, Netherlands.
    Arama, Charles
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Bamako, Mali.
    Giusti, Pablo
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Maiga, Bakary
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Bamako, Mali.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Dolo, Amagana
    Doumbo, Ogobara
    Persson, Jan-Olov
    Stockholms universitet, Naturvetenskapliga fakulteten, Matematiska institutionen.
    Boström, Stephanie
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Haptoglobin phenotype prevalence and cytokine profiles during Plasmodium falciparum infection in Dogon and Fulani ethnic groups living in Mali2013Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 12, s. 432-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The Fulani are known to have a lower parasitaemia and less clinical episodes of malaria as compared to the Dogon sympatric ethnic group, living in Mali. Higher circulating malaria-specific antibody titers and increased pro-inflammatory cytokine levels have been shown in Fulani individuals. Several studies have tried to link haptoglobin (Hp) phenotypes with susceptibility to malaria, but without consensus. This study investigated the role of Hp phenotypes and cytokine levels in Dogon and Fulani during asymptomatic Plasmodium falciparum infection. Methods: Two different cohorts were combined in this study: a 2008 cohort with 77 children aged between two and ten years and a 2001 cohort, with 82 children and adults, aged between 11 and 68 years. Hp phenotypes in plasma were measured by Western Blot. Circulating levels of sCD163, IL-6, IL-10, IFN-gamma and TNF were measured by ELISA. Multiple regression analysis was performed to associate Hp phenotypes with cytokine profiles. In addition, in vitro stimulation of peripheral blood mononuclear cells (PBMCs) with Hp:Hb complexes was performed and cytokine release in corresponding supernatants were measured using cytometric bead array. Results: The results revealed a higher Hp2-2 phenotype prevalence in the Fulani. The Hp2-2 phenotype was associated with a higher susceptibility to P. falciparum infection in Dogon, but not in Fulani. In concordance with previous studies, Fulani showed increased inflammatory mediators (IL-6, IFN-gamma) and additionally also increased sCD163 levels compared to Dogon, irrespective of infection. Furthermore, infected individuals showed elevated sCD163 levels compared to uninfected individuals, in both Fulani and Dogon. Multiple regression analysis revealed that the Hp1-1 phenotype was associated with higher levels of TNF and IFN-gamma, as compared to the Hp2-2 phenotype. In vitro stimulation of PBMCs with Hb:Hp1-1 complexes resulted in a pro-inflammatory cytokine profile, whilst stimulation with Hb: Hp2-2 complexes showed a more balanced profile. Conclusions: Ethnicity might be an important confounder on the Hp phenotype-dependent susceptibility to malaria and future studies could consider taking this into account when designing new immunological studies. Although, the relatively small sample size used in this study warrens for precautions in the interpretation of the data and these findings should ideally be validated in a bigger cohort.

  • 18. Portugal, Silvia
    et al.
    Doumtabe, Didier
    Traore, Boubacar
    Miller, Louis H.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Doumbo, Ogobara K.
    Dolo, Amagana
    Pierce, Susan K.
    Crompton, Peter D.
    B cell analysis of ethnic groups in Mali with differential susceptibility to malaria2012Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 11, s. 162-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Several studies indicate that people of the Fulani ethnic group are less susceptible to malaria compared to those of other ethnic groups living sympatrically in Africa, including the Dogon ethnic group. Although the mechanisms of this protection remain unclear, the Fulani are known to have higher levels of Plasmodium falciparum-specific antibodies of all Ig classes as compared to the Dogon. However, the proportions of B cell subsets in the Fulani and Dogon that may account for differences in the levels of Ig have not been characterized. Methods: In this cross-sectional study, venous blood was collected from asymptomatic Fulani (n = 25) and Dogon (n = 25) adults in Mali during the malaria season, and from P. falciparum-naive adults in the U. S. (n = 8). At the time of the blood collection, P. falciparum infection was detected by blood-smear in 16% of the Fulani and 36% of the Dogon volunteers. Thawed lymphocytes were analysed by flow cytometry to quantify B cell subsets, including immature and naive B cells; plasma cells; and classical, activated, and atypical memory B cells (MBCs). Results: The overall distribution of B cell subsets was similar between Fulani and Dogon adults, although the percentage of activated MBCs was higher in the Fulani group (Fulani: 11.07% [95% CI: 9.317 - 12.82]; Dogon: 8.31% [95% CI: 6.378 - 10.23]; P = 0.016). The percentage of atypical MBCs was similar between Fulani and Dogon adults (Fulani: 28.3% [95% CI: 22.73 - 34.88]; Dogon: 29.3% [95% CI: 25.06 - 33.55], but higher than U. S. adults (U. S.: 3.0% [95% CI: -0.21 - 6.164]; P < 0.001). Plasmodium falciparum infection was associated with a higher percentage of plasma cells among Fulani (Fulani infected: 3.3% [95% CI: 1.788 - 4.744]; Fulani uninfected: 1.71% [95% CI: 1.33 - 2.08]; P = 0.011), but not Dogon adults. Conclusion: These data show that the malaria-resistant Fulani have a higher percentage of activated MBCs compared to the Dogon, and that P. falciparum infection is associated with a higher percentage of plasma cells in the Fulani compared to the Dogon, findings that may account for the higher levels of P. falciparum antibodies in the Fulani.

  • 19. Shelton, Jennifer M. G.
    et al.
    Corran, Patrick
    Risley, Paul
    Silva, Nilupa
    Hubbart, Christina
    Jeffreys, Anna
    Rowlands, Kate
    Craik, Rachel
    Cornelius, Victoria
    Hensmann, Meike
    Molloy, Sile
    Sepulveda, Nuno
    Clark, Taane G.
    Band, Gavin
    Clarke, Geraldine M.
    Spencer, Christopher C. A.
    Kerasidou, Angeliki
    Campino, Susana
    Auburn, Sarah
    Tall, Adama
    Ly, Alioune Badara
    Mercereau-Puijalon, Odile
    Sakuntabhai, Anavaj
    Djimde, Abdoulaye
    Maiga, Boubacar
    Toure, Ousmane
    Doumbo, Ogobara K.
    Dolo, Amagana
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
    Mangano, Valentina D.
    Verra, Frederica
    Modiano, David
    Bougouma, Edith
    Sirima, Sodiomon B.
    Ibrahim, Muntaser
    Hussain, Ayman
    Eid, Nahid
    Elzein, Abier
    Mohammed, Hiba
    Elhassan, Ahmed
    Elhassan, Ibrahim
    Williams, Thomas N.
    Ndila, Carolyne
    Macharia, Alexander
    Marsh, Kevin
    Manjurano, Alphaxard
    Reyburn, Hugh
    Lemnge, Martha
    Ishengoma, Deus
    Carter, Richard
    Karunaweera, Nadira
    Fernando, Deepika
    Dewasurendra, Rajika
    Drakeley, Christopher J.
    Riley, Eleanor M.
    Kwiatkowski, Dominic P.
    Rockett, Kirk A.
    Genetic determinants of anti-malarial acquired immunity in a large multi-centre study2015Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 14, artikel-id 333Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites across Africa and Asia to use standardized methods to look for consistent genetic effects on anti-malarial antibody levels. Methods: Sera, DNA samples and clinical data were collected from 13,299 individuals from ten sites in Senegal, Mali, Burkina Faso, Sudan, Kenya, Tanzania, and Sri Lanka using standardized methods. DNA was extracted and typed for 202 Single Nucleotide Polymorphisms with known associations to malaria or antibody production, and antibody levels to four clinical grade malarial antigens [AMA1, MSP1, MSP2, and (NANP) 4] plus total IgE were measured by ELISA techniques. Regression models were used to investigate the associations of clinical and genetic factors with antibody levels. Results: Malaria infection increased levels of antibodies to malaria antigens and, as expected, stable predictors of anti-malarial antibody levels included age, seasonality, location, and ethnicity. Correlations between antibodies to blood-stage antigens AMA1, MSP1 and MSP2 were higher between themselves than with antibodies to the (NANP)(4) epitope of the pre-erythrocytic circumsporozoite protein, while there was little or no correlation with total IgE levels. Individuals with sickle cell trait had significantly lower antibody levels to all blood-stage antigens, and recessive homozygotes for CD36 (rs321198) had significantly lower anti-malarial antibody levels to MSP2. Conclusion: Although the most significant finding with a consistent effect across sites was for sickle cell trait, its effect is likely to be via reducing a microscopically positive parasitaemia rather than directly on antibody levels. However, this study does demonstrate a framework for the feasibility of combining data from sites with heterogeneous malaria transmission levels across Africa and Asia with which to explore genetic effects on anti-malarial immunity.

  • 20. Tangteerawatana, Piyatida
    et al.
    Perlmann, Hedvig
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Hayano, Masashi
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Kalambaheti, Thareerat
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut, Avdelningen för immunologi.
    Khusmith, Srisin
    IL4 gene polymorphism and previous malaria experiences manipulate anti-Plasmodium falciparum antibody isotype profiles in complicated and uncomplicated malaria.2009Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 8, nr 1, s. 286-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    ABSTRACT: BACKGROUND: The IL4-590 gene polymorphism has been shown to be associated with elevated levels of anti-Plasmodium falciparum IgG antibodies and parasite intensity in the malaria protected Fulani of West Africa. This study aimed to investigate the possible impact of IL4-590C/T polymorphism on anti-P. falciparum IgG subclasses and IgE antibodies levels and the alteration of malaria severity in complicated and uncomplicated malaria patients with or without previous malaria experiences. METHODS: Anti-P.falciparum IgG subclasses and IgE antibodies in plasma of complicated and uncomplicated malaria patients with or without previous malaria experiences were analysed using ELISA. IL4-590 polymorphisms were genotyped using RFLP-PCR. Statistical analyses of the IgG subclasses and IgE levels were done by Oneway ANOVA. Genotype differences were tested by Chi-squared test. RESULTS: The IL4-590T allele was significantly associated with anti-P. falciparum IgG3 antibody levels in patients with complicated (P=0.031), but not with uncomplicated malaria (P=0.622). Complicated malaria patients with previous malaria experiences carrying IL4-590TT genotype had significantly lower levels of anti-P. falciparum IgG3 (P=0.0156), while uncomplicated malaria patients with previous malaria experiences carrying the same genotype had significantly higher levels (P=0.0206) compared to their IL4-590 counterparts. The different anti-P. falciparum IgG1 and IgG3 levels among IL4-590 genotypes were observed. Complicated malaria patients with previous malaria experiences tended to have lower IgG3 levels in individuals carrying TT when compared to CT genotypes (P=0.075). In contrast, complicated malaria patients without previous malaria experiences carrying CC genotype had significantly higher anti-P. falciparum IgG1 than those carrying either CT or TT genotypes (P=0.004, P=0.002, respectively). CONCLUSIONS: The results suggest that IL4-590C or T alleles participated differently in the regulation of anti-malarial antibody isotype profiles in primary and secondary malaria infection and, therefore, could play an important role in alteration of malaria severity.

  • 21. Topalis, Pantelis
    et al.
    Mitraka, Elvira
    Bujila, Ioana
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Deligianni, Elena
    Dialynas, Emmanuel
    Siden-Kiamos, Inga
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Louis, Christos
    IDOMAL: an ontology for malaria2010Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 9, s. 230-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Ontologies are rapidly becoming a necessity for the design of efficient information technology tools, especially databases, because they permit the organization of stored data using logical rules and defined terms that are understood by both humans and machines. This has as consequence both an enhanced usage and interoperability of databases and related resources. It is hoped that IDOMAL, the ontology of malaria will prove a valuable instrument when implemented in both malaria research and control measures. METHODS: The OBOEdit2 software was used for the construction of the ontology. IDOMAL is based on the Basic Formal Ontology (BFO) and follows the rules set by the OBO Foundry consortium. RESULTS: The first version of the malaria ontology covers both clinical and epidemiological aspects of the disease, as well as disease and vector biology. IDOMAL is meant to later become the nucleation site for a much larger ontology of vector borne diseases, which will itself be an extension of a large ontology of infectious diseases (IDO). The latter is currently being developed in the frame of a large international collaborative effort. CONCLUSIONS: IDOMAL, already freely available in its first version, will form part of a suite of ontologies that will be used to drive IT tools and databases specifically constructed to help control malaria and, later, other vector-borne diseases. This suite already consists of the ontology described here as well as the one on insecticide resistance that has been available for some time. Additional components are being developed and introduced into IDOMAL.

  • 22.
    Vafa, Manijeh
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Troye-Blomberg, Marita
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Anchang, Judith
    Garcia, André
    Migot-Nabias, Florence
    Multiplicity of Plasmodium falciparum infection in asymptomatic children in Senegal: relation to transmission, age and erythrocyte variants.2008Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 7, s. 17-Artikel i tidskrift (Refereegranskat)
  • 23.
    Vafa, Manijeh
    et al.
    Stockholms universitet, Naturvetenskapliga fakulteten, Wenner-Grens institut.
    Troye-Blomberg, Marita
    Anchang, Judith
    Garcia, André
    Migot-Nabias, Florence
    Multiplicity of Plasmodium falciparum infection in asymptomatic children in Senegal: relation to transmission, age and erythrocyte variants2008Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 7, nr 17Artikel i tidskrift (Refereegranskat)
  • 24.
    Zacarias, Orlando P.
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap. Eduardo Mondlane University, Moçambique.
    Andersson, Mikael
    Stockholms universitet, Naturvetenskapliga fakulteten, Matematiska institutionen.
    Mapping malaria incidence distribution that accounts for environmental factors in Maputo Province - Mozambique2010Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 9, artikel-id 79Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The objective was to study if an association exists between the incidence of malaria and some weather parameters in tropical Maputo province, Mozambique. Methods: A Bayesian hierarchical model to malaria count data aggregated at district level over a two years period is formulated. This model made it possible to account for spatial area variations. The model was extended to include environmental covariates temperature and rainfall. Study period was then divided into two climate conditions: rainy and dry seasons. The incidences of malaria between the two seasons were compared. Parameter estimation and inference were carried out using MCMC simulation techniques based on Poisson variation. Model comparisons are made using DIC. Results: For winter season, in 2001 the temperature covariate with estimated value of -8.88 shows no association to malaria incidence. In year 2002, the parameter estimation of the same covariate resulted in 5.498 of positive level of association. In both years rainfall covariate determines no dependency to malaria incidence. Malaria transmission is higher in wet season with both covariates positively related to malaria with posterior means 1.99 and 2.83 in year 2001. For 2002 only temperature is associated to malaria incidence with estimated value 2.23. Conclusions: The incidence of malaria in year 2001, presents an independent spatial pattern for temperature in summer and for rainfall in winter seasons respectively. In year 2002 temperature determines the spatial pattern of malaria incidence in the region. Temperature influences the model in cases where both covariates are introduced in winter and summer season. Its influence is extended to the summer model with temperature covariate only. It is reasonable to state that with the occurrence of high temperatures, malaria incidence had certainly escalated in this year.

  • 25.
    Zacarias, Orlando P.
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap. Eduardo Mondlane University, Mozambique.
    Andersson, Mikael
    Stockholms universitet, Naturvetenskapliga fakulteten, Matematiska institutionen.
    Spatial and temporal patterns of malaria incidence in Mozambique2011Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 10, artikel-id 189Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The objective of this study is to analyze the spatial and temporal patterns of malaria incidence as to determine the means by which climatic factors such as temperature, rainfall and humidity affect its distribution in Maputo province, Mozambique. Methods: This study presents a model of malaria that evolves in space and time in Maputo province-Mozambique, over a ten years period (1999-2008). The model incorporates malaria cases and their relation to environmental variables. Due to incompleteness of climatic data, a multiple imputation technique is employed. Additionally, the whole province is interpolated through a Gaussian process. This method overcomes the misalignment problem of environmental variables (available at meteorological stations points) and malaria cases (available as aggregates for every district - area). Markov Chain Monte Carlo (MCMC) methods are used to obtain posterior inference and Deviance Information Criteria (DIC) to perform model comparison. Results: A Bayesian model with interaction terms was found to be the best fitted model. Malaria incidence was associated to humidity and maximum temperature. Malaria risk increased with maximum temperature over 28 degrees C (relative risk (RR) of 0.0060 and 95% Bayesian credible interval (CI) of 0.00033-0.0095) and humidity (relative risk (RR) of 0.00741 and 95% Bayesian CI 0.005141-0.0093). The results would suggest that additional non-climatic factors including socio-economic status, elevation, etc. also influence malaria transmission in Mozambique. Conclusions: These results demonstrate the potential of climate predictors particularly, humidity and maximum temperature in explaining malaria incidence risk for the studied period in Maputo province. Smoothed maps obtained as monthly average of malaria incidence allowed to visualize months of initial and peak transmission. They also illustrate a variation on malaria incidence risk that might not be related to climatic factors. However, these factors are still determinant for malaria transmission and intensity in the region.

  • 26.
    Zacarias, Orlando P.
    et al.
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap. Eduardo Mondlane University, Mozambique .
    Majlender, Peter
    Stockholms universitet, Samhällsvetenskapliga fakulteten, Institutionen för data- och systemvetenskap.
    Comparison of infant malaria incidence in districts of Maputo province, Mozambique2011Ingår i: Malaria Journal, E-ISSN 1475-2875, Vol. 10, artikel-id 93Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Malaria is one of the principal health problems in Mozambique, representing 48% of total external consultations and 63% of paediatric hospital admissions in rural and general hospitals with 26.7% of total mortality. Plasmodium falciparum is responsible for 90% of all infections being also the species associated with most severe cases. The aim of this study was to identify zones of high malaria risk, showing their spatially and temporal pattern. Methods: Space and time Poison model for the analysis of malaria data is proposed. This model allows for the inclusion of environmental factors: rainfall, temperature and humidity as predictor variables. Modelling and inference use the fully Bayesian approach via Markov Chain Monte Carlo (MCMC) simulation techniques. The methodology is applied to analyse paediatric data arising from districts of Maputo province, Mozambique, between 2007 and 2008. Results: Malaria incidence risk is greater for children in districts of Manhica, Matola and Magude. Rainfall and humidity are significant predictors of malaria incidence. The risk increased with rainfall (relative risk - RR: .006761, 95% interval: .001874, .01304), and humidity (RR: .049, 95% interval: .03048, .06531). Malaria incidence was found to be independent of temperature. Conclusions: The model revealed a spatial and temporal pattern of malaria incidence. These patterns were found to exhibit a stable malaria transmission in most non-coastal districts. The findings may be useful for malaria control, planning and management.

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