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7. Independent origin of Plasmodium falciparum antifolate super-resistance, Uganda, Tanzania, and Ethiopia

Author

Alifrangis, Michael, Nag, Sidsel, Schousboe, Mette L., Ishengoma, Deus, Lusingu, John, Pota, Hirva, Kavishe, Reginald A., Pearce, Richard, Ord, Rosalynn, Lynch, Caroline, Dejene, Seyoum, Cox, Jonathan, Rwakimari, John, Minja, Daniel T.R., Lemnge, Martha M., and Roper, Cally

Subjects
Antimalarials -- Usage -- Health aspects, Drug resistance -- Research, Genetic polymorphisms -- Research, Malaria -- Drug therapy, Plasmodium falciparum -- Origin -- Health aspects, Health
Abstract

Controlling and reducing malaria requires a combination of vector control measures and administration of antimalarial drugs as prophylaxis or treatment (1). The widespread use of antimalarial drugs has resulted in [...]

Published
2014
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9. Epidemic of Plasmodium falciparum malaria involving substandard antimalarial drugs, Pakistan, 2003

Author

Leslie, Toby, Kaur, Harparkash, Mohammed, Nasir, Kolaczinski, Kate, Ord, Rosalynn L., and Rowland, Mark

Subjects
Plasmodium falciparum -- Analysis, Antimalarials -- Analysis, Drug resistance -- Analysis, Dihydrofolate reductase -- Analysis, Malaria -- Analysis, Refugees -- Analysis, Anopheles -- Analysis
Abstract

Epidemics make a major contribution to the global impact of malaria (1). Predisposing factors include level of disease endemicity, immune status of the population, changes in vector--person contact, unusual weather [...]

Published
2009
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10. Reduction of Malaria Transmission to Anopheles Mosquitoes with a Six-Dose Regimen of Co-Artemether

Author

Sutherland Colin J, Ord Rosalynn, Dunyo Sam, Jawara Musa, Drakeley Christopher J, Alexander Neal, Coleman Rosalind, Pinder Margaret, Walraven Gijs, and Targett Geoffrey A. T

Subjects
Infectious Diseases, Medicine
Abstract

Background Resistance of malaria parasites to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) is increasing in prevalence in Africa. Combination therapy can both improve treatment and provide important public health benefits if it curbs the spread of parasites harbouring resistance genes. Thus, drug combinations must be identified which minimise gametocyte emergence in treated cases, and so prevent selective transmission of parasites resistant to any of the partner drugs. Methods and Findings In a randomised controlled trial, 497 children with uncomplicated falciparum malaria were treated with CQ and SP (three doses and one dose respectively; n = 91), or six doses of artemether in fixed combination with lumefantrine (co-artemether [Coartem, Riamet]) (n = 406). Carriage rates of Plasmodium falciparum gametocytes and trophozoites were measured 7, 14, and 28 d after treatment. The infectiousness of venous blood from 29 children carrying P. falciparum gametocytes 7 d after treatment was tested by membrane-feeding of Anopheles mosquitoes. Children treated with co-artemether were significantly less likely to carry gametocytes within the 4 weeks following treatment than those receiving CQ/SP (30 of 378 [7.94%] versus 42 of 86 [48.8%]; p < 0.0001). Carriers in the co-artemether group harboured gametocytes at significantly lower densities, for shorter periods (0.3 d versus 4.2 d; p < 0.0001) and were less infectious to mosquitoes at day 7 (p < 0.001) than carriers who had received CQ/SP. Conclusions Co-artemether is highly effective at preventing post-treatment transmission of P. falciparum. Our results suggest that co-artemether has specific activity against immature sequestered gametocytes, and has the capacity to minimise transmission of drug-resistant parasites.

Published
2005
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14. Cluster of falciparum malaria cases in UK airport

Author

Rodger, Alison J., Cooke, Graham S., Ord, Rosalynn, Sutherland, Colin J., and Pasvol, Geoffrey

Subjects
Malaria -- Diagnosis, Travelers, Plasmodium falciparum, Airports
Abstract

A cluster of 6 cases of Plasmodium falciparum malaria occurred in a UK airport among 30 travelers returning to the United States from East Africa. Molecular genotyping analysis indicated that [...]

Published
2008

15. Plasmodium malariae in Haitian refugees, Jamaica

Author

Lindo, John F., Bryce, Jeanette Horner, Ducasse, Marion Bullock, Howitt, Christina, Barrett, Donnett M., Morales, Jacob Lorenzo, Ord, Rosalynn, Burke, Martina, Chiodini, Peter L., and Sutherland, Colin J.

Subjects
Plasmodium falciparum -- Health aspects, Refugees -- Health aspects, Infection -- Health aspects, Disease transmission -- Health aspects, Malaria -- Health aspects
Abstract

Since 1963, reported malaria transmission in Haiti has been restricted to Plasmodium falciparum. However, screening of Haitian refugees in Jamaica in 2004, by microscopic examination, identified P. falciparum, P. vivax, [...]

Published
2007

16. High prevalence of dhfr triple mutant and correlation with high rates of sulphadoxine-pyrimethamine treatment failures in vivo in Gabonese children

Author

Profanter Katharina, Greutélaers Katja C, Gabor Julian J, Ord Rosalynn, Oyakhirome Sunny, Mombo-Ngoma Ghyslain, Greutélaers Benedikt, Kurth Florian, Lell Bertrand, Kun Jürgen FJ, Issifou Saadou, Roper Cally, Kremsner Peter G, and Grobusch Martin P

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Drug resistance contributes to the global malaria burden. Plasmodium falciparum dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) polymorphisms confer resistance to sulphadoxine-pyrimethamine (SP). Methods The study assessed the frequency of SP resistance-conferring polymorphisms in Plasmodium falciparum-positive samples from two clinical studies in Lambaréné. Their role on treatment responses and transmission potential was studied in an efficacy open-label clinical trial with a 28-day follow-up in 29 children under five with uncomplicated malaria. Results SP was well tolerated by all subjects in vivo. Three subjects were excluded from per-protocol analysis. PCR-corrected, 12/26 (46%) achieved an adequate clinical and parasitological response, 13/26 (50%) were late parasitological failures, while 1/26 (4%) had an early treatment failure, resulting in early trial discontinuation. Of 106 isolates, 98 (92%) carried the triple mutant dhfr haplotype. Three point mutations were found in dhps in a variety of haplotypic configurations. The 437G + 540E double mutant allele was found for the first time in Gabon. Conclusions There is a high prevalence of dhfr triple mutant with some dhps point mutations in Gabon, in line with treatment failures observed, and molecular markers of SP resistance should be closely monitored. Trial Registration ClinicalTrials.gov: NCT00453856

Published
2011
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17. A Community-Randomized Evaluation of the Effect of Intermittent Preventive Treatment in Infants on Antimalarial Drug Resistance in Southern Tanzania

Author

Pearce, Richard J., Ord, Rosalynn, Kaur, Haprarksh, Lupala, Cecylia, Schellenberg, Joanna, Shirima, Kitzito, Manzi, Fatuma, Alonso, Pedro, Tanner, Marcel, Mshinda, Hassan, Roper, Cally, and Schellenberg, David

Subjects
parasitic diseases
Abstract

Background. Intermittent preventive treatment in infants (IPTi) is the administration of sulfadoxine-pyrimethamine (SP) at 2, 3, and 9 months of age to prevent malaria. We investigated the influence of IPTi on drug resistance. Methods. Twenty-four areas were randomly assigned to receive or not receive IPTi. Blood collected during representative household surveys at baseline and 15 and 27 months after implementation was tested for SP and resistance markers. Results. The frequency of SP in blood was similar in the IPTi and comparison areas at baseline and at 15 months. dhfr and dhps mutations were also similar at baseline and then increased similarly in both arms after 15 months of SP-IPTi. First-line treatment was switched from SP to artemether-lumefantrine before the final survey, when SP positivity fell among infants in comparison areas but increased in IPTi areas. This was accompanied by an increase in dhfr but not dhps mutations in IPTi areas (P = .004 and P = .18, respectively). Conclusions. IPTi did not increase drug pressure or the selection on dhfr and dhps mutants, when SP was the first-line malaria treatment. Introduction of artemether-lumefantrine was followed by an increase in dhfr mutations, consistent with weak selection attributable to SP-IPTi, but not by an increase in dhps mutations, suggesting a fitness cost of this mutation

Published
2017

18. Sympatric Plasmodium falciparum isolates from Venezuela have structured var gene repertoires

Author

Targett Geoffrey AT, Ord Rosalynn, Tami Adriana, and Sutherland Colin J

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background The human malaria parasite Plasmodium falciparum expresses adhesins belonging to the erythrocyte membrane protein 1 (PfEMP1) family on the surface of the infected host erythrocyte. These antigens elicit a strain-specific antibody response that is associated with protection from disease. During clonal expansion of blood-stage parasites, the surface phenotype of the infected erythrocyte changes because of transcriptional switching among the 40 to 50 members of the highly polymorphic var multi-gene family which encode PfEMP1 variants. Studies to date have compared var repertoires of natural isolates from various geographical locations but have not addressed any within-population structure that may exist among repertoires. Methods Distinct parasite genotypes from a single population co-circulating among a defined group of hosts were selected. PCR products encoding the DBL-α domain of PfEMP-1 were cloned and sequenced from each of three isolates. Repertoire similarity was statistically evaluated using combinatorial analysis. The chromosomal location of shared sequences was inferred from similarity to dbl-α of known location in the 3D7 genome. Results Sympatric parasites were found to share few var gene sequences, even when alleles at other polymorphic loci were shared. A number of the sequences shared by at least two of the isolates studied were found to be related to 3D7 genomic sequences with non-telomeric chromosomal locations, or atypical domain structures, which may represent globally conserved loci. Conclusion The parasite population studied is structured, with minimal overlap in PfEMP1 repertoires. The var gene family accumulates diversity more rapidly than other antigen genes examined. This may be facilitated by ectopic recombination among the sub-telomeric regions of P. falciparum chromosomes.

Published
2003
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21. The Benefits of Artemisinin Combination Therapy for Malaria Extend Beyond the Individual Patient

Author

Sutherland, Colin J, Ord, Rosalynn, Dunyo, Sam, Jawara, Musa, Drakeley, Christopher J, Alexander, Neal, Coleman, Rosalind, Pinder, Margaret, Walraven, Gijs, and Targett, Geoffrey A. T

Subjects
Male, Medicine in Developing Countries, Mosquito Control, Plasmodium falciparum, Infant, Chloroquine, Gametogenesis, Malaria, Antimalarials, Drug Combinations, Infectious Diseases, Pyrimethamine, Child, Preschool, parasitic diseases, Anopheles, Sulfadoxine, Animals, Humans, Female, Single-Blind Method, Malaria, Falciparum, Child, Research Article
Abstract

Background Resistance of malaria parasites to chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) is increasing in prevalence in Africa. Combination therapy can both improve treatment and provide important public health benefits if it curbs the spread of parasites harbouring resistance genes. Thus, drug combinations must be identified which minimise gametocyte emergence in treated cases, and so prevent selective transmission of parasites resistant to any of the partner drugs. Methods and Findings In a randomised controlled trial, 497 children with uncomplicated falciparum malaria were treated with CQ and SP (three doses and one dose respectively; n = 91), or six doses of artemether in fixed combination with lumefantrine (co-artemether [Coartem, Riamet]) (n = 406). Carriage rates of Plasmodium falciparum gametocytes and trophozoites were measured 7, 14, and 28 d after treatment. The infectiousness of venous blood from 29 children carrying P. falciparum gametocytes 7 d after treatment was tested by membrane-feeding of Anopheles mosquitoes. Children treated with co-artemether were significantly less likely to carry gametocytes within the 4 weeks following treatment than those receiving CQ/SP (30 of 378 [7.94%] versus 42 of 86 [48.8%]; p < 0.0001). Carriers in the co-artemether group harboured gametocytes at significantly lower densities, for shorter periods (0.3 d versus 4.2 d; p < 0.0001) and were less infectious to mosquitoes at day 7 (p < 0.001) than carriers who had received CQ/SP. Conclusions Co-artemether is highly effective at preventing post-treatment transmission of P. falciparum. Our results suggest that co-artemether has specific activity against immature sequestered gametocytes, and has the capacity to minimise transmission of drug-resistant parasites., Do treatment regimens in malaria also affect transmission of parasites? In this African trial co-artemether worked significantly better than the chloroquine and sulphadoxine- pyrimethamine together

Published
2005

22. Global and local genetic diversity at two microsatellite loci in Plasmodium vivax parasites from Asia, Africa and South America

Author

Schousboe, Mette L, primary, Ranjitkar, Samir, additional, Rajakaruna, Rupika S, additional, Amerasinghe, Priyanie H, additional, Konradsen, Flemming, additional, Morales, Francisco, additional, Ord, Rosalynn, additional, Pearce, Richard, additional, Leslie, Toby, additional, Rowland, Mark, additional, Gadalla, Nahla, additional, Bygbjerg, Ib C, additional, Alifrangis, Michael, additional, and Roper, Cally, additional

Published
2014
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25. Independent Origin ofPlasmodium falciparumAntifolate Super-Resistance, Uganda, Tanzania, and Ethiopia

Author

Alifrangis, Michael, primary, Nag, Sidsel, additional, Schousboe, Mette L., additional, Ishengoma, Deus, additional, Lusingu, John, additional, Pota, Hirva, additional, Kavishe, Reginald A., additional, Pearce, Richard, additional, Ord, Rosalynn, additional, Lynch, Caroline, additional, Dejene, Seyoum, additional, Cox, Jonathan, additional, Rwakimari, John, additional, Minja, Daniel T.R., additional, Lemnge, Martha M., additional, and Roper, Cally, additional

Published
2014
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26. Sympatric Plasmodium falciparum isolates from Venezuela have structured var gene repertoires

Author

Tami, Adriana, Ord, Rosalynn, Targett, Geoffrey A T, and Sutherland, Colin J

Subjects
Adult, Male, lcsh:Arctic medicine. Tropical medicine, Adolescent, Genotype, lcsh:RC955-962, Genes, Protozoan, Plasmodium falciparum, Protozoan Proteins, Antigens, Protozoan, lcsh:Infectious and parasitic diseases, Malaria, Falciparum/epidemiology, Protein Structure, Tertiary/genetics, Gene Frequency, Animals, Humans, lcsh:RC109-216, Malaria, Falciparum, Conserved Sequence, Merozoite Surface Protein 1, Genetics, Population/statistics & numerical data, Research, Plasmodium falciparum/genetics, Genetic Variation, DNA, Protozoan, Venezuela, Protein Structure, Tertiary, Cross-Sectional Studies, Genetics, Population, Gene Frequency/genetics, Antigens, Protozoan/genetics, Protozoan Proteins/genetics, Conserved Sequence/genetics, DNA, Protozoan/genetics, Merozoite Surface Protein 1/genetics, Venezuela/epidemiology
Abstract

Background The human malaria parasite Plasmodium falciparum expresses adhesins belonging to the erythrocyte membrane protein 1 (PfEMP1) family on the surface of the infected host erythrocyte. These antigens elicit a strain-specific antibody response that is associated with protection from disease. During clonal expansion of blood-stage parasites, the surface phenotype of the infected erythrocyte changes because of transcriptional switching among the 40 to 50 members of the highly polymorphic var multi-gene family which encode PfEMP1 variants. Studies to date have compared var repertoires of natural isolates from various geographical locations but have not addressed any within-population structure that may exist among repertoires. Methods Distinct parasite genotypes from a single population co-circulating among a defined group of hosts were selected. PCR products encoding the DBL-α domain of PfEMP-1 were cloned and sequenced from each of three isolates. Repertoire similarity was statistically evaluated using combinatorial analysis. The chromosomal location of shared sequences was inferred from similarity to dbl-α of known location in the 3D7 genome. Results Sympatric parasites were found to share few var gene sequences, even when alleles at other polymorphic loci were shared. A number of the sequences shared by at least two of the isolates studied were found to be related to 3D7 genomic sequences with non-telomeric chromosomal locations, or atypical domain structures, which may represent globally conserved loci. Conclusion The parasite population studied is structured, with minimal overlap in PfEMP1 repertoires. The var gene family accumulates diversity more rapidly than other antigen genes examined. This may be facilitated by ectopic recombination among the sub-telomeric regions of P. falciparum chromosomes.

Published
2003

27. Analysis of Polymorphisms in the Merozoite Surface Protein-3a Gene and Two Microsatellite Loci in Sri Lankan Plasmodium vivax: Evidence of Population Substructure in Sri Lanka

Author

Schousboe, Mette L, Rajakaruna, Rupika S, Amerasinghe, Priyanie H, Konradsen, Flemming, Ord, Rosalynn, Pearce, Richard, Bygbjerg, Ib C, Roper, Cally, Alifrangis, Michael, Schousboe, Mette L, Rajakaruna, Rupika S, Amerasinghe, Priyanie H, Konradsen, Flemming, Ord, Rosalynn, Pearce, Richard, Bygbjerg, Ib C, Roper, Cally, and Alifrangis, Michael

Abstract

The geographical distribution of genetic variation in Plasmodium vivax samples (N = 386) from nine districts across Sri Lanka is described using three markers; the P. vivax merozoite surface protein-3a (Pvmsp-3a) gene, and the two microsatellites m1501 and m3502. At Pvmsp-3a, 11 alleles were found with an expected heterozygosity (H(e)) of 0.81, whereas at m1501 and m3502, 24 alleles (H(e) = 0.85) and 8 alleles (H(e) = 0.74) were detected, respectively. Overall, 95 unique three locus genotypes were detected among the 279 samples positive at all three loci (H(e) = 0.95). Calculating the pairwise fixation index (F(ST)) revealed statistically significant population structure. The presence of identical 2-loci microsatellite genotypes in a significant proportion of samples revealed local clusters of closely related isolates contributing to strong linkage disequilibrium between marker alleles. The results show evidence of high genetic diversity and possible population substructure of P. vivax populations in Sri Lanka.

Published
2011

28. A Community-Randomized Evaluation of the Effect of Intermittent Preventive Treatment in Infants on Antimalarial Drug Resistance in Southern Tanzania

Author

Pearce, Richard J., primary, Ord, Rosalynn, additional, Kaur, Haprarksh, additional, Lupala, Cecylia, additional, Schellenberg, Joanna, additional, Shirima, Kitzito, additional, Manzi, Fatuma, additional, Alonso, Pedro, additional, Tanner, Marcel, additional, Mshinda, Hassan, additional, Roper, Cally, additional, and Schellenberg, David, additional

Published
2012
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31. Analysis of Polymorphisms in the Merozoite Surface Protein-3α Gene and Two Microsatellite Loci in Sri Lankan Plasmodium vivax: Evidence of Population Substructure in Sri Lanka

Author

Schousboe, Mette L., primary, Konradsen, Flemming, additional, Amerasinghe, Priyanie H., additional, Rajakaruna, Rupika S., additional, Roper, Cally, additional, Bygbjerg, Ib C., additional, Pearce, Richard, additional, Ord, Rosalynn, additional, and Alifrangis, Michael, additional

Published
2011
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32. High prevalence of dhfr triple mutant and correlation with high rates of sulphadoxine-pyrimethamine treatment failures in vivo in Gabonese children

Author

Mombo-Ngoma, Ghyslain, primary, Oyakhirome, Sunny, additional, Ord, Rosalynn, additional, Gabor, Julian J, additional, Greutélaers, Katja C, additional, Profanter, Katharina, additional, Greutélaers, Benedikt, additional, Kurth, Florian, additional, Lell, Bertrand, additional, Kun, Jürgen FJ, additional, Issifou, Saadou, additional, Roper, Cally, additional, Kremsner, Peter G, additional, and Grobusch, Martin P, additional

Published
2011
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34. Monitoring for multidrug-resistantPlasmodium falciparumisolates and analysis of pyrimethamine resistance evolution in Uige province, Angola

Author

Menegon, Michela, primary, Pearce, Richard J., additional, Inojosa, Walter O., additional, Pisani, Vincenzo, additional, Abel, Paulo M., additional, Matondo, Alexandre, additional, Bisoffi, Zeno, additional, Majori, Giancarlo, additional, Ord, Rosalynn, additional, Warhurst, David C., additional, Roper, Cally, additional, and Severini, Carlo, additional

Published
2009
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35. Multiple Origins and Regional Dispersal of Resistant dhps in African Plasmodium falciparum Malaria

Author

Pearce, Richard J., primary, Pota, Hirva, additional, Evehe, Marie-Solange B., additional, Bâ, El-Hadj, additional, Mombo-Ngoma, Ghyslain, additional, Malisa, Allen L., additional, Ord, Rosalynn, additional, Inojosa, Walter, additional, Matondo, Alexandre, additional, Diallo, Diadier A., additional, Mbacham, Wilfred, additional, van den Broek, Ingrid V., additional, Swarthout, Todd D., additional, Getachew, Asefaw, additional, Dejene, Seyoum, additional, Grobusch, Martin P., additional, Njie, Fanta, additional, Dunyo, Samuel, additional, Kweku, Margaret, additional, Owusu-Agyei, Seth, additional, Chandramohan, Daniel, additional, Bonnet, Maryline, additional, Guthmann, Jean-Paul, additional, Clarke, Sian, additional, Barnes, Karen I., additional, Streat, Elizabeth, additional, Katokele, Stark T., additional, Uusiku, Petrina, additional, Agboghoroma, Chris O., additional, Elegba, Olufunmilayo Y., additional, Cissé, Badara, additional, A-Elbasit, Ishraga E., additional, Giha, Hayder A., additional, Kachur, S. Patrick, additional, Lynch, Caroline, additional, Rwakimari, John B., additional, Chanda, Pascalina, additional, Hawela, Moonga, additional, Sharp, Brian, additional, Naidoo, Inbarani, additional, and Roper, Cally, additional

Published
2009
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37. High Resistance of Plasmodium falciparum to Sulphadoxine/Pyrimethamine in Northern Tanzania and the Emergence of dhps Resistance Mutation at Codon 581

Author

Gesase, Samwel, primary, Gosling, Roly D., additional, Hashim, Ramadhan, additional, Ord, Rosalynn, additional, Naidoo, Inbarani, additional, Madebe, Rashid, additional, Mosha, Jacklin F., additional, Joho, Angel, additional, Mandia, Victor, additional, Mrema, Hedwiga, additional, Mapunda, Ephraim, additional, Savael, Zacharia, additional, Lemnge, Martha, additional, Mosha, Frank W., additional, Greenwood, Brian, additional, Roper, Cally, additional, and Chandramohan, Daniel, additional

Published
2009
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40. Plasmodium malariaein Haitian Refugees, Jamaica

Author

Lindo, John F., primary, Bryce, Jeanette Horner, additional, Ducasse, Marion Bullock, additional, Howitt, Christina, additional, Barrett, Donnett M., additional, Morales, Jacob Lorenzo, additional, Ord, Rosalynn, additional, Burke, Martina, additional, Chiodini, Peter L., additional, and Sutherland, Colin J., additional

Published
2007
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41. SUSTAINED USE OF INSECTICIDE-TREATED CURTAINS IS NOT ASSOCIATED WITH GREATER CIRCULATION OF DRUG-RESISTANT MALARIA PARASITES, OR WITH HIGHER RISK OF TREATMENT FAILURE AMONG CHILDREN WITH UNCOMPLICATED MALARIA IN BURKINA FASO

Author

DIALLO, DIADIER A., primary, POTA, HIRVA, additional, ORD, ROSALYNN, additional, KONATÉ, AMADOU T., additional, COUSENS, SIMON N., additional, ILBOUDO-SANOGO, EDITH, additional, ROPER, CALLY, additional, NEBIÉ, ISSA, additional, GREENWOOD, BRIAN M., additional, and SUTHERLAND, COLIN, additional

Published
2007
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43. Chloroquine/Sulphadoxine-Pyrimethamine for Gambian Children with Malaria: Transmission to Mosquitoes of Multidrug-Resistant Plasmodium falciparum

Author

Hallett, Rachel L, primary, Dunyo, Samuel, additional, Ord, Rosalynn, additional, Jawara, Musa, additional, Pinder, Margaret, additional, Randall, Anna, additional, Alloueche, Ali, additional, Walraven, Gijs, additional, Targett, Geoffrey A. T, additional, Alexander, Neal, additional, and Sutherland, Colin J, additional

Published
2006
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44. Randomised Trial of Chloroquine/Sulphadoxine-Pyrimethamine in Gambian Children with Malaria: Impact against Multidrug-Resistant P. falciparum

Author

Dunyo, Samuel, primary, Ord, Rosalynn, additional, Hallett, Rachel, additional, Jawara, Musa, additional, Walraven, Gijs, additional, Mesa, Eduardo, additional, Coleman, Rosalind, additional, Sowe, Maimuna, additional, Alexander, Neal, additional, Targett, Geoffrey A. T, additional, Pinder, Margaret, additional, and Sutherland, Colin J, additional

Published
2006
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50. Identification and Characterization of the Rhoptry Neck Protein 2 in Babesia divergensand B. microti

Author

Ord, Rosalynn L., Rodriguez, Marilis, Cursino-Santos, Jeny R., Hong, Hyunryung, Singh, Manpreet, Gray, Jeremy, and Lobo, Cheryl A.

Abstract

ABSTRACTApicomplexan parasites include those of the genera Plasmodium, Cryptosporidium, and Toxoplasmaand those of the relatively understudied zoonotic genus Babesia. In humans, babesiosis, particularly transfusion-transmitted babesiosis, has been emerging as a major threat to public health. Like malaria, the disease pathology is a consequence of the parasitemia which develops through cyclical replication of Babesiaparasites in host erythrocytes. However, there are no exoerythrocytic stages in Babesia, so targeting of the blood stage and associated proteins to directly prevent parasite invasion is the most desirable option for effective disease control. Especially promising among such molecules are the rhoptry neck proteins (RONs), whose homologs have been identified in many apicomplexan parasites. RONs are involved in the formation of the moving junction, along with AMA1, but no RON has been identified and characterized in any Babesiaspp. Here we identify the RON2 proteins of Babesia divergens(BdRON2) and B. microti(BmRON2) and show that they are localized apically and that anti-BdRON2 antibodies are significant inhibitors of parasite invasion in vitro. Neither protein is immunodominant, as both proteins react only marginally with sera from infected animals. Further characterization of the direct role of both BdRON2 and BmRON2 in parasite invasion is required, but knowledge of the level of conformity of RON2 proteins within the apicomplexan phylum, particularly that of the AMA1-RON2 complex at the moving junction, along with the availability of an animal model for B. microtistudies, provides a key to target this complex with a goal of preventing the erythrocytic invasion of these parasites and to further our understanding of the role of these conserved ligands in invasion.

Published
2016
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