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  • 1. Amodu, O. K.
    et al.
    Olaniyan, S. A.
    Adeyemo, A. A.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Olumese, P. E.
    Omotade, O. O.
    Association of the sickle cell trait and the ABO blood group with clinical severity of malaria in southwest Nigeria2012In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 123, no 2, p. 72-77Article in journal (Refereed)
    Abstract [en]

    In regions of high Plasmodium falciparum malaria endemicity, certain erythrocyte polymorphisms confer resistance to severe disease. In this study, we evaluate the role of the sickle cell trait (HbS) and ABO blood groups in the clinical manifestations of childhood malaria in Southwest Nigeria. The subjects comprised 3100 children (53% males, median age 39 months), including 1400 children with uncomplicated malaria, 1000 children with asymptomatic malaria and 700 with severe malaria. Haemoglobin (Hb) types were determined using electrophoresis and serum agglutination techniques were used to determine ABO blood groups. Blood group O was the commonest ABO blood group (47.7%) in the study population, the others were A (22.5%), B (25.2%) and AB (4.6%). The frequencies of the HbAS and HbAC were 14.4% and 5.8%, respectively. In regression models adjusting for age, gender, parasite density and blood group, HbAS was associated with a reduced risk of severe malaria OR=0.46 (CI95%: 0.273-0.773). Among severe malaria subjects, HbAS was associated with significantly lower parasite densities. The protective effect of blood group 0 was demonstrated with a decreased risk of severe malaria OR=0.743 (CI95%: 0.566-0.976) after adjusting for age, gender and parasite density and Hb genotype. Blood group B was associated with increased risk of severe malaria OR=1.638 (CI95%: 1.128-2.380) after adjusting for age, gender, packed cell volume, parasite density and Hb genotype. We have confirmed from this large study of Nigerian children the major protective effective of the sickle cell heterozygous state against both cerebral malaria and severe malarial anaemia. We also show that the B blood group is associated with an increased risk of severe malaria. In conclusion, the sickle cell haemoglobin type and ABO groups modulate the risk of severe malaria in Nigerian children.

  • 2. Arama, Charles
    et al.
    Maiga, Bakary
    Dolo, Amagana
    Kouriba, Bourema
    Traore, Boubacar
    Crompton, Peter D.
    Pierce, Susan K.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Miller, Louis H.
    Doumbo, Ogobara K.
    Ethnic differences in susceptibility to malaria: What have we learned from immuno-epidemiological studies in West Africa?2015In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 146, p. 152-156Article, review/survey (Refereed)
    Abstract [en]

    There are many fundamental aspects of the immunobiology of Plasmodium falciparum infections that are not fully understood, therefore limiting our comprehension of how people become immune to malaria and why some ethnic groups living in malaria endemic areas are less susceptible than others. The complexity of parasite-host interactions and the genetic diversity of the parasites as well as the human host complicate our strategy to address this issue. In this mini-review we discuss and summarize what we have learned about African ethnic differences in susceptibility to malaria from immuno-epidemiological studies. Additionally, we suggest research topics that might be of great value for dissecting the mechanisms of protection by providing new insights into molecular interactions between the parasite and the host.

  • 3. Arrighi, Romanico B. G.
    et al.
    Faye, Ingrid
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Plasmodium falciparum GPI toxin: A common foe for man and mosquito2010In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 114, no 3, p. 162-165Article in journal (Refereed)
    Abstract [en]

    The glycosylphosphatidylinositol (GPI) anchor of the malaria parasite, Plasmodium falciparum, which can be regarded as an endotoxin, plays a role in the induced pathology associated with severe malaria in humans. However, it is unclear whether the main mosquito vector, Anopheles gambiae, can specifically recognize, and respond to GPI from the malaria parasite. Recent data suggests that the malaria vector does mount a specific response against malaria GPI. In addition, following the strong immune response, mosquito fecundity is severely affected, resulting in a significant reduction in viable eggs produced. In this mini-review we look at the increased interest in understanding the way that malaria antigens are recognized in the mosquito, and how this relates to a better understanding of the interactions between the malaria parasite and both human and vector.

  • 4.
    Awah, Nancy W.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Gysin, Jürg
    Unité de Parasitologie Expérimentale, URA Institut Pasteur/Univ-Med.
    Mechanisms of malarial anaemia: potential involvement of the Plasmodium falciparum low molecular weight rhoptry-associated proteins.2009In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 112, no 3, p. 295-302Article in journal (Refereed)
    Abstract [en]

    Plasmodium falciparum malaria is a major cause of morbidity and mortality throughout the tropics. Anaemia is a constant feature of the disease. Pregnant women mostly primigravidae and children below the age of 5 years are the most afflicted. Its pathogenesis is multifactorial and incompletely understood. Among several factors, the destruction of erythrocytes (RBCs) is the most frequently observed cause of severe malarial anaemia and the removal of non-parasitized RBCs (nEs) is thought to be the most important, accounting for approximately 90% of the reduction in haematocrit in acute malaria. Previous studies demonstrated that the tagging of nEs with the parasite antigen RAP-2 (rhoptry-associated protein-2; also designated RSP-2) due to either failed or aborted invasion by merozoites resulted in the destruction of these cells. In this study we further investigated the mechanisms mediating the destruction of nEs in the development of severe malarial anaemia and the possible involvement of RAP-2/RSP-2 and other members of the low molecular weight rhoptry complex (RAP-1: rhoptry-associated protein-1 and RAP-3: rhoptry-associated protein-3). Antibodies to the rhoptry-associated proteins were found to recognise the surface of nEs in a parasitaemia-dependent manner after merozoite release in P. falciparumin vitro cultures. These cells, as well as erythroblasts co-cultured with infected RBCs (IEs), could then be destroyed by either phagocytosis or lysis after complement activation. The ability of anti-rhoptry antibodies to mediate the destruction of RAP-2/RSP-2-tagged erythroblasts in the presence of effector cells was also investigated. Data obtained suggest that mouse monoclonal antibodies to the low molecular weight RAP proteins mediate the death of RAP-2/RSP-2-tagged erythroblasts on interaction with adherent monocytes. The mechanism of cell death is not yet fully known, but seems to involve primarily apoptosis. The above observations suggest that the antibody response against RAP-2/RSP-2 and other members of the complex could trigger the destruction of RAP-2/RSP-2-tagged host cells. Taken together it appears that during severe anaemia a defective bone marrow or dyserythropoiesis possibly due to erythroblast cell death, may overlap with the accelerated destruction of normal erythroid cells, either by opsonisation or complement activation further aggravating the anaemia which may become fatal. These observations could therefore have implications in the design, development and deployment of future therapeutic interventions against malaria.

  • 5.
    Balogun, Halima A.
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Awah, Nancy
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Nilsson, Sandra
    Rogier, Christophe
    Trape, Jean-Francois
    Chen, Qijun
    Roussilhon, Christian
    Berzins, Klavs
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Pattern of antibodies to the Duffy binding like domain of Plasmodium falciparum antigen Pf332 in Senegalese individuals2014In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 130, p. 80-87Article in journal (Refereed)
    Abstract [en]

    Acquisition of antibodies against blood stage antigens is crucial in malaria immunity and the Plasmodium falciparum antigen Pf332, which is present in close association with the infected red blood cell membrane, is one such antigen. In this study, the antibody response to a Duffy binding like fragment of Pf332, termed Pf332-DBL was investigated in sera from naturally exposed individuals living in Dielmo village, Senegal, with regard to immunoglobulin classes (IgG, IgM, IgE) and IgG subclasses (IgG1-4). While the levels of IgM, IgG, IgG1 and IgG2 only displayed a moderate trend to increase with age, Pf332-DBL specific IgG3 levels increased significantly in the older villagers. In multivariate analysis, when controlling for confounding factors, and in a linear model with a Poisson distribution, anti-Pf332-DBL IgG3 as well as the ratio of cytophilic to non cytophilic anti-Pf332-DBL antibodies were found significantly associated with a reduced risk of malaria attack. This association was also present when the IgG3:IgG1 ratio was tested. Finally, two subgroups of villagers with the same mean age, were delineated by IgG3 concentrations either lower or higher than the median value. A total of 45.2% of the individuals with low anti-Pf332-DBL-IgG3 levels but only 21.4% of the villagers in the group with high levels of such antibodies had a clinical malaria attack during a period of 3 years of continuous follow-up after the blood sampling. In conclusion, Pf332-DBL induces naturally the acquisition of antibodies, and Pf332-DBL-specific IgG3 appears to be associated with protection against malaria in this endemic setting.

  • 6.
    Bolad, A K
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Nebie, I
    Esposito, F
    Berzins, Klavs
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    The use of impregnated curtains does not affect antibody responses against Plasmodium falciparum and complexity of infecting parasite populations in children from Burkina Faso2004In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 90, no 3, p. 237-247Article in journal (Refereed)
    Abstract [en]

    In Burkina Faso, where malaria is hyper-endemic and transmission intensity is very high, the majority of malaria-related morbidity and mortality occurs in children less than 5 years of age. A control measure such as the use of insecticide-treated curtains (ITC) significantly reduces transmission of malaria infection. Concerns remain whether reduced transmission intensity may lead to a delay in the development of immunity in younger children and even to a partial loss of already acquired immunity. In this study, the levels of P. falciparum-specific IgG subclasses, the number of infecting parasite clones determined by PCR-based genotyping of the msp2 gene and the parasite density were analysed in 154 asymptomatic children (3–6 years) living in 16 villages (8 with and 8 without ITC) in the vicinity of Ouagadougou, the capital of Burkina Faso. In addition, the parasite inhibitory effects of Ig fractions, prepared from selected children, in co-operation with normal human monocytes were studied. Blood samples from asymptomatic ITC-users showed a significant decrease in P. falciparum prevalence as well as in parasite density. However, no significant difference was observed in P. falciparum-specific antibodies or in parasite multiplicity of infection between the two groups. Furthermore, Ig fractions from children of both groups showed similar levels of inhibitory activity against autologous parasite growth both on their own and in co-operation with monocytes.

  • 7. Bwijo, B
    et al.
    Kaneko, A
    Takechi, M
    Zungu, I.L.
    Moriyama, Y
    Lum, J.K.
    Tsukahara, T.
    Mita, T
    Takahashi, N
    Bergqvist, Yngve
    Dalarna University, School of Technology and Business Studies, Chemical Engineering.
    Björkman, A
    Kobayakawa, T
    High prevalence of quintuple mutant dphps/dhfr genes in Plasmodium falciparum infections seven years after introduction of sulfadoxine and Pyrimethamine as first line treatment in Malawi2003In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, no 85, p. 363-373Article in journal (Refereed)
  • 8. Cherif, Mariama K.
    et al.
    Sanou, Guillaume S.
    Bougouma, Edith C.
    Diarra, Amidou
    Ouedraogo, Alphonse
    Dolo, Amagana
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Cavanagh, David R.
    Theisen, Michael
    Modiano, David
    Sirima, Sodiomon B.
    Nebie, Issa
    Is Fc gamma receptor IIA (Fc gamma RIIA) polymorphism associated with clinical malaria and Plasmodium falciparum specific antibody levels in children from Burkina Faso?2015In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 142, p. 41-46Article in journal (Refereed)
    Abstract [en]

    In the present study, the influences of Fc gamma RIIA polymorphism on susceptibility to malaria and antibody responses to Plasmodium falciparum antigens were analyzed in children. We recruited 96 healthy children between 3 and 10 years at the beginning of the high transmission season and we followed up for 5 months through the high transmission season to assess the parasitological, immunological and genetic endpoints in relation to clinical malaria status. There was a similar distribution of homozygous and heterozygous individuals carrying the Fc gamma RIIA-131R/R and Fc gamma RIIA-131R/H allele, whereas the number of Fc gamma RIIA-131H/H homozygous individuals was lower. P. falciparum infection frequency was not associated with the Fc gamma RIIa-131R/H polymorphism. Only IgG antibody responses to GLURP R0 showed a significant association between antibody levels and Fc gamma RIIA polymorphism (p = 0.02). IgG levels to MSP2a were significantly higher in children who did not experience any clinical malaria episode compared to those who experienced at least one malaria episode (p = 0.019). Cytophilic and non-cytophylic IgG subclass levels were higher in children without malaria than those who experienced at least one malaria episode. This difference was statistically significant for IgG1 to MSP3 (p = 0.003) and to MSP2a (p = 0.006); IgG3 to MSP2a (p = 0.007) and to GLURP R0 (p = 0.044); IgG2 to MSP2b (p = 0.007) and IgG4 to MSP3 (p = 0.051) and to MSP2a (p = 0.049). In this study, homozygous carriers of the Fc gamma RIIA-131R/R allele had higher malaria-specific antibody levels compare to the heterozygous carriers Fc gamma RIIA-131R/H alleles and to homozygous carriers of Fc gamma RIIA-131H/H alleles. The pre-existing antibodies responses were related to a reduced subsequent risk of clinical malaria.

  • 9. Gicheru, Michael
    et al.
    Jeneby, Maamun
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Macharia, J.C.
    Carlsson, Hans-Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Suleman, Mbaruk
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Comparative Medicine.
    Prevalence of antibodies and cell mediated immune responce against Leishmania major in feral non-human primates from Kenya2009In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 109, no 2, p. 136-140Article in journal (Refereed)
    Abstract [en]

    In Kenya, Leishmania major is responsible for human cutaneous leishmaniasis (CL). Natural infection with L. major of a vervet monkey and experimental susceptibility of some nonhuman primates (NHPs) from Kenya has been established. However, there has been no comprehensive study of the prevalence of zoonotic CL in Kenya. And also, no investigation has been done to assess whether NHPs could be potential reservoir hosts of L. major even when the involvement of reservoir animals is obligatory in transmission of this parasite. To achieve this, wild caught Chlorocebus aethiops (Vervet monkeys n=213), Papio cynocephalus anubis (olive baboons n=101) and Cercopithecus mitis (Syke's monkeys n=64) from five geographical locations in Kenya were screened for antibodies against L. major using enzyme linked immunosorbent assay (ELISA) and Western blot (WB) analysis. From the population of C. aethiops (n=213) captured, 57 were used in lymphocyte proliferation assay. ELISA revealed a high prevalence of leishmaniasis sero conversion in olive baboons 78/101 (77.2%), vervet monkeys 129/213 (60.6%) and Sykes' monkeys 43/64 (67.2%). WB detected anti-L. major antibodies in 48.5% (49/101) of the baboons, 48% (102/213) of vervet monkeys and 37.5% (24/64) of Sykes' monkey sera. Specific proliferation of peripheral blood mononuclear cells to L. major antigen was demonstrated in 17 of the 57 (29.8%) vervet monkeys. In conclusion, the results of serological assays provide strong circumstantial evidence that CL is prevalent in five Provinces of Kenya and that Kenyan NHPs could be could be a potential reservoir hosts of L. major.

  • 10.
    Guadalupe Ortega-Pierres, M.
    et al.
    IPN, Ctr Invest & Estudios Avanzados, Dept Genet & Mol Biol, Mexico City, DF, Mexico..
    Jex, Aaron R.
    Walter & Eliza Hall Inst Med Res, Populat Hlth & Immun Div, Parkville, Vic, Australia.;Univ Melbourne, Fac Vet & Agr Sci, Parkville, Vic, Australia..
    Ansell, Brendan R. E.
    Univ Melbourne, Fac Vet & Agr Sci, Parkville, Vic, Australia..
    Svärd, Staffan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Microbiology.
    Recent advances in the genomic and molecular biology of Giardia2018In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 184, p. 67-72Article in journal (Refereed)
    Abstract [en]

    Giardia duodenalis is the most common gastrointestinal protozoan parasite of humans and a significant contributor to the global burden of both diarrheal disease and post-infectious chronic disorders. Robust tools for analyzing gene function in this parasite have been developed and a range of genetic tools are now available. These together with public databases have provided insights on the function of different genes in Giardia. In this review we provide a current perspective on different molecular aspects of Giardia related to genomics, regulation of encystation, trophozoite transcriptional responses to physiological and xenobiotic (drug-induced) stress, and mechanisms of drug resistance. We also examine recent insights that have contributed to gain knowledge in the study of VSPs, antigenic variation, epigenetics, DNA repair and in the direct manipulation of gene function in Giardia, with a particular focus on the inducible Cre/loxP system.

  • 11. Hugosson, Elisabeth
    et al.
    Montgomery, Scott M.
    Örebro University, Department of Clinical Medicine.
    Premji, Zul
    Troye-Blomberg, Marita
    Björkman, Anders
    Relationship between antipyretic effects and cytokine levels in uncomplicated falciparum malaria during different treatment regimes2006In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 99, no 1, p. 75-82Article in journal (Refereed)
    Abstract [en]

    We have previously shown that both chloroquine and paracetamol (acetaminophen) have antipyretic activity during treatment of acute uncomplicated Plasmodium falciparum malaria in children 1-4 years old. Here, we studied if this effect was accompanied by changes in plasma cytokine levels. The 104 children were treated with either chloroquine or sulfadoxine/pyrimethamine (SP) alone, SP+chloroquine or SP+paracetamol for 4 days. Cytokine levels were determined days 0, 2 and 3, body temperature every sixth hour until 72h and parasitemia once daily for 4 days. At admission, body temperature correlated with levels of IL-10, IFN-gamma and IL-6, and parasitemia correlated with IL-10 and IL-6. Except for TNF-alpha and IL-1beta, where no significant effect was found, all cytokine levels (IL-10, IFN-gamma, IL-6, IL-12, IL-13, IL-18 and IL-4) decreased up to day 2 (p<0.05). IL-6 levels continued to fall from days 2 to 3 (p<0.05), whereas increased levels were found for several cytokines (IL-12, IL-13, IL-18 and IL-1beta) (p<0.05). The antipyretic effects of chloroquine and paracetamol could not be related to any specific changes in the evaluated cytokine production or in Th1/Th2 or inflammatory/anti-inflammatory cytokine ratios. Alternative mechanisms for antipyretic effects and associations between fever and cytokine levels during uncomplicated P. falciparum malaria are therefore discussed.

  • 12. Kamugisha, Erasmus
    et al.
    Bujila, Ioana
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Lahdo, Mona
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Pello-Esso, Samtou
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Minde, Mercy
    Kongola, Gilbert
    Naiwumbwe, Halima
    Kiwuwa, Steven
    Kaddumukasa, Mark
    Kironde, Fred
    Swedberg, Göte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Large differences in prevalence of Pfcrt and Pfmdr1 mutations between Mwanza, Tanzania and Iganga, Uganda: a reflection of differences in policies regarding withdrawal of chloroquine?2012In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 121, no 2, p. 148-151Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Malaria is still a major public health problem in the world and sub-Saharan Africa is one of the most affected areas. Efforts to control malaria are highly affected by drug resistance to commonly used antimalarials. The introduction of artemisinin based combination therapy (ACT) as a first line drug seems to be a major step in treatment of uncomplicated malaria, though search for drugs to combine with artemisinins still continues. There have been reports on increased prevalence of the wild type markers Pfcrt 76K and Pfmdr1 86N in some African countries and ideas of using chloroquine (CQ) in intermittent presumptive treatment for adults (IPTa) is coming up. The common combination of artemether and lumefantrine even selects for parasites that are wild type at these positions. This study is comparing prevalence of mutation at these two positions in two East African countries with ACT as their first line drug but following somewhat different drug policies regarding CQ. In Tanzania CQ was stopped in 2001 but in Uganda CQ was retained in combination with sulfadoxine-pyrimethamine (SP) and used in home based management of fever for some time. SP is still used in IPT for pregnant women.

    METHODS:

    Blood smears and dried blood spots on Whatman filter papers were collected from 100 patients with uncomplicated malaria in Mwanza, Tanzania and 100 patients from Iganga, Uganda. DNA was extracted from all samples using Tris EDTA method. PCR and RFLP were performed and sequencing done on Pfcrt amplification products.

    RESULTS:

    The prevalence of K76T mutations at Pfcrt in samples from Mwanza, Tanzania was 40.5% (34/84) and 100% (100/100) in samples from Iganga, Uganda. Prevalence of N86Y mutations in Pfmdr1 was 16.9% (13/77) and 77.7% (63/81) in samples from Mwanza and Iganga, respectively. The re-emergence of CQ sensitive isolates in Mwanza, Tanzania showed the haplotype CVMNK typical for wild type isolates.

    CONCLUSIONS:

    The prevalence of CQ resistant parasites in Mwanza, Tanzania is low compared to the existing high level of resistant parasites in Iganga, Uganda. This could be an indication that CQ may become useful in the future in Tanzania. This study shows clearly that there is a difference in mutations at these positions in these two countries implementing similar but somewhat different drug policies. In Uganda the drug resistance has reached fixation while in Tanzania the prevalence is going down.

  • 13. Kamugisha, Erasmus
    et al.
    Bujila, Ioana
    Department of Medical Biochemistry and Microbiology, Uppsala University, Sweden.
    Lahdo, Mona
    Pello-Esso, Samtou
    Minde, Mercy
    Kongola, Gilbert
    Naiwumbwe, Halima
    Kiwuwa, Steven
    Kaddumukasa, Mark
    Kironde, Fred
    Swedberg, Göte
    Large differences in prevalence of Pfcrt and Pfmdr1 mutations between Mwanza, Tanzania and Iganga, Uganda-a reflection of differences in policies regarding withdrawal of chloroquine?2012In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 121, no 2, p. 148-151Article in journal (Refereed)
    Abstract [en]

    Background: Malaria is still a major public health problem in the world and sub-Saharan Africa is one of the most affected areas. Efforts to control malaria are highly affected by drug resistance to commonly used antimalarials. The introduction of artemisinin based combination therapy (ACT) as a first line drug seems to be a major step in treatment of uncomplicated malaria, though search for drugs to combine with artemisinins still continues. There have been reports on increased prevalence of the wild type markers Pfcrt 76K and Pfmdr1 86N in some African countries and ideas of using chloroquine (CQ) in intermittent presumptive treatment for adults (IPTa) is coming up. The common combination of artemether and lumefantrine even selects for parasites that are wild type at these positions. This study is comparing prevalence of mutation at these two positions in two East African countries with ACT as their first line drug but following somewhat different drug policies regarding CQ. In Tanzania CQ was stopped in 2001 but in Uganda CQ was retained in combination with sulfadoxine-pyrimethamine (SP) and used in home based management of fever for some time. SP is still used in IPT for pregnant women.

    Methods: Blood smears and dried blood spots on Whatman filter papers were collected from 100 patients with uncomplicated malaria in Mwanza, Tanzania and 100 patients from Iganga, Uganda. DNA was extracted from all samples using Tris EDTA method. PCR and RFLP were performed and sequencing done on Pfcrt amplification products.

    Results: The prevalence of K76T mutations at Pfcrt in samples from Mwanza, Tanzania was 40.5% (34/84) and 100% (100/100) in samples from Iganga, Uganda. Prevalence of N86Y mutations in Pfmdr1 was 16.9% (13/77) and 77.7% (63/81) in samples from Mwanza and Iganga, respectively. The re-emergence of CQ sensitive isolates in Mwanza, Tanzania showed the haplotype CVMNK typical for wild type isolates.

    Conclusions: The prevalence of CQ resistant parasites in Mwanza, Tanzania is low compared to the existing high level of resistant parasites in Iganga, Uganda. This could be an indication that CQ may become useful in the future in Tanzania. This study shows clearly that there is a difference in mutations at these positions in these two countries implementing similar but somewhat different drug policies. In Uganda the drug resistance has reached fixation while in Tanzania the prevalence is going down.

  • 14.
    Kaneko, Akira
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    A community-directed strategy for sustainable malaria elimination on islands: Short-term MDA integrated with ITNs and robust surveillance2010In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 114, no 3, p. 177-183Article in journal (Refereed)
    Abstract [en]

    In the Asia Pacific sites with low and unstable transmission, elimination should be feasible with existing tools. On Aneityum island, Vanuatu both Plasmodium falciparum and Plasmodium vivax malaria were eliminated in 1991 after implementation of a combined intervention package, including mass drug administration (MDA) and insecticide-treated bed nets (ITNs), with high degree of community involvement. Subsequently, community-based surveillance and vector control measures have kept. By reviewing the experiences of the Aneityum project, I intended to examine the roles of community in malaria elimination. To be successful, the program should transfer major intervention components from the external donor-directed initiative to the community-directed approach. Scaling up of community involvement from simple participation to social participation, where communities involve in health planning functions is necessary from malaria control to malaria elimination.

  • 15. Kumsiri, Ratchanok
    et al.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Pattanapanyasat, Kovit
    Krudsood, Srivicha
    Maneerat, Yaowapa
    IgE low affinity receptor (CD23) expression, Plasmodium falciparum specific IgE and tumor necrosis factor-alpha production in Thai uncomplicated and severe falciparum malaria patients2016In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 154, p. 25-33Article in journal (Refereed)
    Abstract [en]

    Previous studies have suggested that Plasmodium falciparum (P. falciparum) specific IgE in the form of immune complexes crosslinking the low-affinity receptor (CD23) on monocyte results in tumor necrosis factor (TNF)-alpha and nitric oxide (NO) production. However, the roles of these parameters in severity and immune protection are still unclear. This study aimed to determine the association between CD23 expression on monocytes, plasma soluble CD23 (sCD23), total IgE, malaria-specific IgE and IgG, and TNF-alpha levels in P. falciparum infected patients. We evaluated 64 uncomplicated (UC) and 25 severe patients (S), admitted at the Hospital for Tropical Diseases, Mahidol University, and 34 healthy controls (C) enrolled in 2001. Flow cytometry and enzyme linked immunosorbent assays (ELISA) demonstrated that trends of the CD23 expression, levels of sCD23 and specific IgE were higher in the S group as compared to those in the UC and C groups. Plasma levels of P. falciparum specific IgE in the UC (p = 0.011) and S groups (p = 0.025) were significantly higher than those in C group. In contrast the TNF-alpha levels tended to be higher in the UC than those in the S (p = 0343) and significantly higher than those in C (p = 0.004) groups. The specific IgG levels in UC were significantly higher than those in S and C (p < 0.001) groups. At admission, a strong significant negative correlation was found between specific IgG and sCD23 (r = -0.762, p = 0.028), and TNF-alpha and IgE-IgG complexes (r=-0.715, p = 0.002). Significant positive correlations between levels of specific IgE and TNF-alpha (r=0.575, p = 0.010); and sCD23 (r=0.597, p = 0.000) were also observed. In conclusion, our data suggest that CD23 expression and malaria-specific IgE levels may be involved in the severity of the disease while TNF-alpha and the malaria-specific IgG may correlate with protection against falciparum malaria.

  • 16. Lebbad, Marianne
    et al.
    Ankarklev, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Tellez, Aleyda
    Leiva, Byron
    Andersson, Jan O.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Svärd, Staffan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology.
    Dominance of Giardia assemblage B in León, Nicaragua.2008In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 106, no 1, p. 44-53Article in journal (Refereed)
    Abstract [en]

    Giardiasis is a major problem in León, Nicaragua, yet despite this no data are available regarding the prevalence of different Giardia genotypes in this area. To address this question, a molecular analysis of Giardia isolates from humans and dogs living in the same area in León, Nicaragua was performed. Giardia isolates from 119 Nicaraguan patients and 8 dogs were successfully genotyped using single and/or nested beta-giardin PCR with subsequent restriction length fragment polymorphism (RFLP) analysis. The analyses of human samples yielded 94 (79%) assemblage B isolates and 25 (21%) assemblage A isolates. Only the non-human-associated assemblages C and D were found in the dog samples. Sixteen isolates with assemblage A pattern, 26 isolates with assemblage B pattern and all dog isolates were further characterized by sequencing the nested beta-giardin PCR product and by molecular analyses of the glutamate dehydrogenase (gdh) gene. Within the study area the assemblage A isolates were highly genetically homogenous, showing only sub-genotypes A2 (n=3) or A3 (n=13) at the beta-giardin locus and AII only at the gdh locus while assemblage B showed a high genetic polymorphism at both loci. Seven different sub-genotypes were identified within 13 of the sequenced assemblage B beta-giardin isolates. The remaining 13 sequenced assemblage B-isolates appeared to contain several different variants of the beta-giardin gene since the chromatograms displayed one to seven double peaks. The gdh sequences showed an even higher polymorphism since only 2 of 26 assemblage B isolates were without double peaks. Two mixed infections between assemblage A and B were found when the gdh gene was analyzed. Polymorphisms were also observed in the dog-associated assemblages C and D, but to a lesser extent than in assemblage B.

  • 17. Lees, Rosemary Susan
    et al.
    Knols, Bart
    Bellini, Romeo
    Benedict, Mark Q.
    Bheecarry, Ambicadutt
    Bossin, Herve Christophe
    Chadee, Dave D.
    Charlwood, Jacques
    Dabire, Roch K.
    Djogbenou, Luc
    Egyir-Yawson, Alexander
    Gato, Rene
    Gouagna, Louis Clement
    Hassan, Mo'awia Mukhtar
    Khan, Shakil Ahmed
    Koekemoer, Lizette L.
    Lemperiere, Guy
    Manoukis, Nicholas C.
    Mozuraitis, Raimondas
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Pitts, R. Jason
    Simard, Frederic
    Gilles, Jeremie R. L.
    Review: Improving our knowledge of male mosquito biology in relation to genetic control programmes2014In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 132, p. S2-S11Article, review/survey (Refereed)
    Abstract [en]

    The enormous burden placed on populations worldwide by mosquito-borne diseases, most notably malaria and dengue, is currently being tackled by the use of insecticides sprayed in residences or applied to bednets, and in the case of dengue vectors through reduction of larval breeding sites or larviciding with insecticides thereof. However, these methods are under threat from, amongst other issues, the development of insecticide resistance and the practical difficulty of maintaining long-term community-wide efforts. The sterile insect technique (SIT), whose success hinges on having a good understanding of the biology and behaviour of the male mosquito, is an additional weapon in the limited arsenal against mosquito vectors. The successful production and release of sterile males, which is the mechanism of population suppression by SIT, relies on the release of mass-reared sterile males able to confer sterility in the target population by mating with wild females. A five year Joint FAO/IAEA Coordinated Research Project brought together researchers from around the world to investigate the pre-mating conditions of male mosquitoes (physiology and behaviour, resource acquisition and allocation, and dispersal), the mosquito mating systems and the contribution of molecular or chemical approaches to the understanding of male mosquito mating behaviour. A summary of the existing knowledge and the main novel findings of this group is reviewed here, and further presented in the reviews and research articles that form this Acta Tropica special issue.

  • 18.
    Lindh, J. M.
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Borg-Karlson, A. -K
    Faye, Ingrid
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Transstadial and horizontal transfer of bacteria within a colony of Anopheles gambiae (DipteraCulicidae) and oviposition response to bacteria-containing water:  2008In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 107, no 3, p. 242-250Article in journal (Refereed)
    Abstract [en]

    In a paratransgenic approach, genetically modified bacteria are utilized to kill the parasite in the vector gut. A critical component for paratransgenics against malaria is how transgenic bacteria can be introduced and then kept in a mosquito population. Here, we investigated transstadial and horizontal transfer of bacteria within an Anopheles gambiae mosquito colony with the focus on spiked breeding sites as a possible means of introducing bacteria to mosquitoes. A Pantoea stewartii strain, previously isolated from An. gambiae, marked with a green fluorescent protein (GFP), was introduced to mosquitoes in different life stages. The following life stages or older mosquitoes in the case of adults were screened for bacteria in their guts. In addition to P. stewartii other bacteria were isolated from the guts: these were identified by 16S rRNA sequence analysis and temporal temperature gradient gel electrophoresis (TTGE). Bacteria were transferred from larvae to pupae but not from pupae to adults. The mosquitoes were able to take up bacteria from the water they emerged from and transfer the same bacteria to the water they laid eggs in. Eliza-bethkingia meningoseptica was more often isolated from adult mosquitoes than P. stewartii. A bioassay was used to examine An. gambiae oviposition responses towards bacteria-containing solutions. The volatiles emitted from the solutions were sampled by headspace-solid phase microextraction (SPME) and identified by gas chromatography and mass spectrometry (GC-MS) analysis. P. stewartii but not E. meningoseptica mediated a positive oviposition response. The volatiles emitted by P stewartii include indole and 3-methyl-1 -butanol, which previously have been shown to affect An. gambiae mosquito behaviour. E. meningoseptica emitted indole but not 3-methyl-1 -butanol, when suspended in saline. Taken together, this indicates that it may be possible to create attractive breeding sites for distribution of genetically modified bacteria in the field in a paratransgenic approach against malaria. Further research is needed to determine if the bacteria are also transferred in the same way in nature.

  • 19.
    Lindh, Jenny M.
    et al.
    Dept of Genetics, Microbiology and Toxicology, Stockholm University.
    Terenius, Olle
    Dept of genetics microbiology and toxicology, Stockholm University.
    Eriksson-Gonzales, Karolina
    Dept of Genetics, Microbiology and Toxicology, Stockholm University.
    Knols, Bart G. J.
    Faye, Ingrid
    Dept of genetics microbiology and toxicology, Stockholm University.
    Re-introducing bacteria in mosquitoes - A method for determination of mosquito feeding preferences based on coloured sugar solutions2006In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 99, no 2-3, p. 173-183Article in journal (Refereed)
    Abstract [en]

    In this study, sugar-feeding was investigated as a possible means of re-introducing bacteria into mosquito midguts with the aim of identifying bacteria that are suitable for creating paratransgenic mosquitoes. In a paratransgenic approach, bacteria are utilised to deliver effector molecules capable of inhibiting pathogen development in the midgut of the vector. To determine if mosquitoes discriminate between sterile sugar solutions and sugar solutions with bacteria, a method for screening mosquito feeding preferences was developed. This method was tested for Aedes aegypti, Anopheles arabiensis and An. gambiae s.s. mosquitoes and is based on a dual-choice test of solutions labelled with food dyes. Three different tests (dye/colour detection, sugar detection and sugar-concentration detection) were performed to evaluate the method, after which bacteria previously isolated from mosquitoes were used in the experiments. It was shown that mosquitoes do not discriminate between sugar solutions with or without these bacteria indicating that sugar-feeding is a possible means to introduce bacteria into mosquitoes. Furthermore, two different setups of the method were used, enabling us to differentiate between tactile/taste and olfactory responses. The method described in this paper is easy to use, cost-effective and allows broad screening of mosquito sugar-feeding preferences.

  • 20.
    Lindh, Jenny
    et al.
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Borg-Karlson, Anna-Karin
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Faye, I.
    Transstadial and horizontal transfer of bacteria within a colony of Anopheles gambiae (Diptera: Culicidae) and oviposition response to bacteria-containing water2008In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 107, no 3, p. 242-250Article in journal (Refereed)
    Abstract [en]

    In a paratransgenic approach, genetically modified bacteria are utilized to kill the parasite in the vector gut. A critical component for paratransgenics against malaria is how transgenic bacteria can be introduced and then kept in a mosquito population. Here, we investigated transstadial and horizontal transfer of bacteria within an Anopheles gambiae mosquito colony with the focus on spiked breeding sites as a possible means of introducing bacteria to mosquitoes. A Pantoea stewartii strain, previously isolated from An. gambiae, marked with a green fluorescent protein (GFP), was introduced to mosquitoes in different life stages. The following life stages or older mosquitoes in the case of adults were screened for bacteria in their guts. In addition to P. stewartii other bacteria were isolated from the guts: these were identified by 16S rRNA sequence analysis and temporal temperature gradient gel electrophoresis (TTGE). Bacteria were transferred from larvae to pupae but not from pupae to adults. The mosquitoes were able to take up bacteria from the water they emerged from and transfer the same bacteria to the water they laid eggs in. Eliza-bethkingia meningoseptica was more often isolated from adult mosquitoes than P. stewartii. A bioassay was used to examine An. gambiae oviposition responses towards bacteria-containing solutions. The volatiles emitted from the solutions were sampled by headspace-solid phase microextraction (SPME) and identified by gas chromatography and mass spectrometry (GC-MS) analysis. P. stewartii but not E. meningoseptica mediated a positive oviposition response. The volatiles emitted by P stewartii include indole and 3-methyl-1 -butanol, which previously have been shown to affect An. gambiae mosquito behaviour. E. meningoseptica emitted indole but not 3-methyl-1 -butanol, when suspended in saline. Taken together, this indicates that it may be possible to create attractive breeding sites for distribution of genetically modified bacteria in the field in a paratransgenic approach against malaria. Further research is needed to determine if the bacteria are also transferred in the same way in nature.

  • 21. Mogensen, Christian B.
    et al.
    Sörensen, Jeff
    Björkman, Anders
    Montgomery, Scott M.
    Örebro University, Department of Clinical Medicine.
    Algorithm for the diagnosis of anaemia without laboratory facilities among small children in a malaria endemic area of rural Tanzania2006In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 99, no 2-3, p. 119-125Article in journal (Refereed)
    Abstract [en]

    BACKGROUND:

    Anaemia among small children in tropical Africa is common and often caused by infection with Plasmodium falciparum. The diagnosis of anaemia is difficult without a laboratory estimation of haemoglobin. The aim of this study was to examine if clinical findings related to malaria and anaemia would help to detect moderate and/or severe anaemia in children in rural Tanzania.

    METHODS:

    Children between 6 and 36 months were examined by health workers in an Out Patient Department (OPD) to detect severe anaemia (packed cell volume, PCV< or =20%) and in a cross sectional survey at village level to identify moderate anaemia (PCV 21-25%). History of recent fever and treatments was recorded and a clinical examination was performed.

    FINDINGS:

    In the survey, comparison of 65 moderately anaemic children with 373 mild/non anaemic children revealed no differences in history of fever or in the clinical examination. In the OPD comparison of 100 severely anaemic children with 116 non-severely anaemic control children revealed that pallor, respiratory rate, number of fever days last week, deteriorated general condition, heart rate, age, splenomegaly, low body weight and elevated body temperature were all indicators of severe 'anaemia, only pallor, respiratory rate, fever days and palpable spleen however, remained associated with severe anaemia in multiple regression analysis. The combination of any pallor and either respiratory rate >55/min or fever >3 days, could predict severe anaemia with a sensitivity of 96% and a specificity of 71%. This was better than the currently recommended signs of severe pallor or an approximation of the Integrated Management of Childhood Illness (IMCI) criteria's for referral of children.

    INTERPRETATION:

    At primary health care level detection of severe anaemia can be improved by information about fever duration and determination of respiratory rate in children with pallor.

  • 22.
    Nyakeriga, Alice M.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology. Texas Tech University, USA; Kilifi District Hospital, Kenya.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Immunology.
    Haptoglobin phenotypes and iron status in children living in a malaria endemic area of Kenyan coast2013In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 126, no 2, p. 127-131Article in journal (Refereed)
    Abstract [en]

    Malaria infection may be affected by host genetic factors as well as nutritional status. Iron status and the phenotype of haptoglobin, a heme-binding acute phase reactant may be determinants of malaria parasitemia. A combination of cross sectional studies and longitudinal follow-up were used to describe the association between iron status, C-reactive protein, malaria infections and host genetic factors including; haptoglobin (Hp) phenotypes, in children below 9 years in a malaria endemic area in Coastal Kenya. The prevalence of 0.45 and 0.41, respectively for Hp 1-1 and Hp 2-1 phenotypes was significantly higher than 0.14 for Hp 2-2 phenotype (n = 162). Children with Hp 2-2 phenotype showed significantly higher iron storage compared to those with Hp 1-1 and Hp 2-1 phenotypes when children with malaria parasites and high C-reactive protein (>9 mg/L) were excluded from the analysis. There were no significant differences in malaria parasite densities among Hp phenotypes but children with Hp 2-2 had lower number of clinical malaria episodes (P=0.045). Taken together, this study shows that the presence of malaria may complicate the interpretation of iron status in children based on their Hp-phenotypes. Further studies will be required to address possible interactions among the various genetic factors and iron status in a malaria endemic setting.

  • 23. Olaniyan, Subulade A.
    et al.
    Amodu, Olukemi K.
    Bakare, Adekunle A.
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Omotade, Olayemi O.
    Rockett, Kirk A.
    Tumour necrosis factor alpha promoter polymorphism, TNF-238 is associated with severe clinical outcome of falciparum malaria in Ibadan southwest Nigeria2016In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 161, p. 62-67Article in journal (Refereed)
    Abstract [en]

    Tumour necrosis factor (TNF) - alpha has been shown to play an important role in the pathogenesis of falciparum malaria. Two TNF promoter polymorphisms, TNF-308 and TNF-238 have been associated with differential activity and production of TNF. In order to investigate the association between TNF-308 and TNF-238 and the clinical outcome of malaria in a Nigerian population, the two TNF polymorphisms were analysed using Sequenom iPLEX Platform. A total of 782 children; 283 children with uncomplicated malaria, 255 children with severe malaria and 244 children with asymptomatic infection (controls) were studied. The distribution of TNF-308 and TNF-238 genotypes were consistent with the Hardy-Weinberg equilibrium. Distribution of both TNF polymorphisms differed significantly across all clinical groups (TNF-308: p = 0.007; TNF-238: p=0.001). Further tests for association with severe malaria using genotype models controlling for age, parasitaemia and HbAS showed a significant association of the TNF-238 polymorphism with susceptibility to severe malaria (95% CI = 1.43-6.02, OR= 2.94, p = 0.003237) The GG genotype of TNF-238 significantly increased the risk of developing cerebral malaria from asymptomatic malaria and uncomplicated malaria (95% CI = 1.99-18.17, OR= 6.02, p <0.001 and 95% CI= 1.78-8.23, OR= 3.84, p <0.001 respectively). No significant association was found between TNF-308 and malaria outcome. These results show thegenetic association of TNF-238 in the clinical outcome of malaria in Ibadan, southwest Nigeria. These findings add support to the role of TNF in the outcome of malaria infection. Further large scale studies across multiple malaria endemic populations will be required to determine the specific roles of TNF-308 and TNF-238 in the outcome of falciparum malaria infection.

  • 24. Pitts, R. Jason
    et al.
    Mozuraitis, Raimondas
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Gauvin-Bialecki, Anne
    Lempérière, Guy
    The roles of kairomones, synomones and pheromones in the chemically-mediated behaviour of male mosquitoes2014In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 132, no 1, p. S26-S34Article in journal (Refereed)
    Abstract [en]

    Despite decades of intensive study of the chemical ecology of female mosquitoes, relatively little is known about the chemical ecology of males. This short review summarizes the current state of knowledge of the chemicals that mediate male mosquito behaviour. Various trophic interactions including insect plant, insect host, and insect insect responses are emphasized. The relevance of the chemical ecology of male mosquitoes in the context of vector control programmes is discussed.

  • 25. Shome, Rajeswari
    et al.
    Deka, Ram Pratim
    Milesh, Ligi
    Sahay, Swati
    Grace, Delia
    Lindahl, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Coxiella seroprevalence and risk factors in large ruminants in Bihar and Assam, India.2019In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 194, p. 41-46Article in journal (Refereed)
    Abstract [en]

    Coxiellosis is a zoonotic disease caused by the ubiquitous bacteria Coxiella burnetii, which can be spread either through ticks or through body fluids. In humans the infection is characterized by a febrile disease; ruminants may abort and reduce their milk yield, causing serious production losses for the farmer. In India, the disease has been known to be present since the 1970s, but little is known about the epidemiology in most states. In this cross-sectional survey in the two states of Assam and Bihar, 520 households were interviewed for risk factors, and serum samples from 744 dairy animals were analyzed using ELISA as well as PCR. Out of the farms, 17.4% had at least one seropositive animal, with significantly higher seroprevalence in Bihar (27.1%) than Assam (5.8%); and significantly more sero-positive farms in urban areas (23.1%) than rural (12.2%). On an individual animal level, 14.1% were seropositive, with higher prevalence among buffaloes than cows (28.0% versus 13.6%). Out of the seropositive animals, 10.6% had aborted during the last three years, and 37.5% had experienced problems with repeat breeding: both higher than in non-seropositive animals. In conclusion, this study indicates that coxiellosis is potentially an important cause of reproductive failures and production losses in dairy animals. The high prevalence, especially in urban areas, is a public health risk. Further research is needed to elucidate the epidemiology and identify mitigation options that could work in the different settings of different Indian states.

  • 26.
    Simone, Olivia
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Bejarano, Maria Teresa
    Pierce, Susan K
    Antonaci, Salvatore
    Wahlgren, Mats
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Donati, Daria
    TLRs innate immunereceptors and Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) CIDR1α-driven human polyclonal B-cell activation.2011In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 119, no 2-3, p. 144-150Article in journal (Refereed)
    Abstract [en]

    Chronic malaria severely affects the immune system and causes polyclonal B-cell activation, as evidenced by the presence of hypergammaglobulinemia, elevated levels of autoantibodies, loss of B-cell memory and the frequent occurrence of Burkitt's lymphomas (BL) in children living in malaria endemic areas. Previous studies have shown that the cysteine-rich interdomain region 1α (CIDR1α) of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) of the FCR3S1.2 strain, subsequently named CIDR1α, interacts with B cells partially through the binding to the B-cell receptor (BCR). This interaction leads to an activated phenotype, increased survival, and a low degree of proliferation. CIDR1α preferentially activates the memory B-cell compartment, therefore PfEMP1 is considered to act as a polyclonal B-cell activator and its role in memory maintenance has been suggested. In this report, we extend the analysis of the PfEMP1-CIDR1α B-cell interaction and demonstrate that PfEMP1-CIDR1α increases the expression of TLR7 and TLR10 mRNA transcripts and sensitizes B cells to TLR9 signalling via the MyD88 adaptor molecule. Furthermore, despite its ability to bind to surface Igs, PfEMP1-CIDR1α-induced B-cell activation does not seem to proceed through the BCR, since it does not induce Lyn and/or phospho-tyrosine mediated signalling pathways. Rather PfEMP1-CIDR1α induces the phosphorylation of downstream kinases, such as ERK1/2, p38 and IKBα, in human B cells. These findings indicate that PfEMP1-CIDR1α induces a persistent activation of B cells, which in turn can contribute to the exhaustion and impairment of B-cell functions during chronic malaria infection.

  • 27.
    Tran, Anh-Nhi
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Andersson, Björn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Pettersson, Ulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Åslund, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Genetics and Pathology.
    Trypanothione synthetase locus in Trypanosoma cruzi CL Brener strain shows an extensive allelic divergence2003In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 87, no 2, p. 269-278Article in journal (Refereed)
    Abstract [en]

    The protozoan parasite Trypanosoma cruzi, agent of Chagas' disease, displays an extensive genetic heterogeneity among strains and isolates. It is, therefore, important to determine the degree of polymorphism in potential candidates for drug design. Our studies on the organisation of the locus containing the gene encoding trypanothione synthetase (TcTRS) (an enzyme involved in the unique trypanothione pathway and hence a promising drug target) revealed a high degree of sequence polymorphism between the two alleles in the T. cruzi CL Brener strain, the reference clone for the genome project. The genes linked to the synthetase appeared to be involved in diverse cell-functions, not part of the trypanothione metabolism. The gene synteny was conserved at both allelic loci that were found to reside on a pair of homologous chromosomes with a size difference of about 2 Mb. The allelic polymorphism of TcTRS resulted in a protein sequence divergence of 4%, ten-times higher than in trypanothione reductase (TR), another key enzyme in the same pathway. Such allelic divergence observed in T. cruzi genes might have implications for drug design against Chagas' disease and the evolutional impact of the CL Brener strain.

  • 28.
    Vafa, Manijeh
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Israelsson, Elisabeth
    Maiga, Bakary
    Dolo, Amagana
    Doumbo, Ogobara K.
    Troye-Blomberg, Marita
    Relationship between immunoglobulin isotype response to Plasmodium falciparum blood stage antigens and parasitological indexes as well as splenomegaly in sympatric ethnic groups living in Mali2009In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 9, no 1, p. 12-16Article in journal (Refereed)
    Abstract [en]

    This study aimed to assess correlations between anti-malarial antibody levels and differences in malariometric characteristics, seen between two sympatric ethnic groups, the Fulani and the Dogon, living in Mali. Plasma levels of anti-malarial IgE, IgG. IgG1-4 and total IgE were determined in asymptomatic individuals, of the above mentioned groups, and were correlated to malariometric indexes. Significantly higher levels of anti-malarial IgE, IgG, IgG1-3 and total IgE were detected in the Fulani individuals as compared to the Dogon. No difference in plasma levels of malaria specific IgG4 was noted between the two groups. Within the Fulani, an increase in total IgE levels was associated with the presence of infection. As the IgG4 level increased, the number of clones decreased in the Fulani individuals. A positive correlation between elevated levels of anti-malarial IgG and IgG3 and splenomegaly was noted only within the Fulani group. No other correlations between antibody levels and parasite prevalence, clone numbers or spleen rates were observed in any of the communities. These results suggest that the magnitude of antibody response against Plasmodium falciparum may not be as important as it is believed to be. Instead, the fine specificity or function of the response might be more critical in protection against malaria disease.

  • 29. Vongsombath, Chanda
    et al.
    de Boer, Hugo J.
    Pålsson, Katinka
    KTH, School of Chemical Science and Engineering (CHE), Chemistry, Organic Chemistry.
    Keeping leeches at bay: Field evaluation of plant-derived extracts against terrestrial blood-sucking leeches (Haemadipsidae) in Lao PDR2011In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 119, no 2-3, p. 178-182Article in journal (Refereed)
    Abstract [en]

    Terrestrial blood-sucking leeches (Haemadipsidae) are common in the damp forests of the subtropical and tropical Indo-Pacific region. Members of the genus Haemadipsa are abundant in Laos and adjacent countries of Southeast Asia, and discomfort to people and livestock. Plant-derived repellents against arthropods and leeches are common in Lao PDR, and have been used by Lao ethnic groups for generations. Numerous studies have been conducted on the efficacy of traditional plant-derived repellents against mosquitoes but only a few on repellents against terrestrial blood-sucking leeches. Field experiments were conducted to evaluate the leech repellent activities of aqueous extracts of three traditionally used plant species, Sapindus rarak DC., Catunaregam spathulifolia Tirv. and Vernonia elaeagnifolia DC. Stockings impregnated with aqueous extracts exhibited moderate to high leech repellent activity, C spathulifolia (62.6%), V. elaeagmfolia (63.0%), and S. rarak (82.6%). The corresponding repellencies of deltamethrin and DEET were 73.1% and 88.4%, respectively. An aqueous extract of S. rarak applied on cloth at a concentration of 1.9 mg/cm(2) is an effective and practical prevention method significantly reducing the number of blood-feeding leeches recorded on stockings worn by humans. This plant species is common in Southeast Asia and can be obtained at limited or no cost.

  • 30.
    Vongsombath, Chanda
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    De Boer, Hugo J.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Pålsson, Katinka
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Keeping Leeches at Bay: Field Evaluation of Plant-Derived Extracts against Terrestrial Blood-Sucking Leeches (Haemadipsidae) in Lao PDR2011In: Acta Tropica, ISSN 0001-706X, E-ISSN 1873-6254, Vol. 119, no 2-3, p. 178-182Article in journal (Refereed)
    Abstract [en]

    Terrestrial blood-sucking leeches (Haemadipsidae) are common in the damp forests of the subtropicaland tropical Indo-Pacific region. Members of the genus Haemadipsa are abundant in Laos and adjacentcountries of Southeast Asia, and discomfort to people and livestock. Plant-derived repellents againstarthropods and leeches are common in Lao PDR, and have been used by Lao ethnic groups for generations.Numerous studies have been conducted on the efficacy of traditional plant-derived repellents againstmosquitoes but only a few on repellents against terrestrial blood-sucking leeches. Field experimentswere conducted to evaluate the leech repellent activities of aqueous extracts of three traditionally usedplant species, Sapindus rarak DC., Catunaregam spathulifolia Tirv. and Vernonia elaeagnifolia DC. Stockingsimpregnated with aqueous extracts exhibited moderate to high leech repellent activity, C. spathulifolia(62.6%), V. elaeagnifolia (63.0%), and S. rarak (82.6%). The corresponding repellencies of deltamethrin andDEET were 73.1% and 88.4%, respectively. An aqueous extract of S. rarak applied on cloth at a concentrationof 1.9 mg/cm2 is an effective and practical prevention method significantly reducing the number of bloodfeedingleeches recorded on stockings worn by humans. This plant species is common in Southeast Asiaand can be obtained at limited or no cost.

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